The coupling of biological entities with electrodes has already quite some history and has reached a status which is not only based on phenomenological descriptions. Nowadays, we are able to effectively couple redox centres within protein molecules to electrochemical transducers. This allows the transduction of a biochemical reaction into an electrode signal with applications mainly in sensing and bioenergetics [1,2,3,4,5,6,7,8]. However, in most cases, this coupling is not direct, and shuttle molecules or side products of the reaction are used. But also for the direct coupling, significant progress has been made, and several enzymes and redox proteins can be addressed directly by electrodes [8,9,10,11,12,13]. The understanding of the functioning of developed systems is, however, in its infancy. Charge and electrostatic interactions have been mostly studied, and for small dipole molecules such as cytochrome c, the situation can be well described [14]. There is a lack of understanding for more complex enzyme molecules which brings a lot of trial and error into research.

The last decade was characterised by an explosion of new materials, which can be used to immobilise protein molecules to electrode surfaces. Particularly, material in the nanoscale appears as a valuable tool since the size dimensions which are similar to biomolecules bring new features and very often avoid inactivation processes occurring by non-biological materials in the macroscale [15,16,17,18,19,20,21]. Unfortunately, the literature is full of systems with several mixed materials and biomolecules, but the role of every single component is often not clear. We need more fundamental studies on the interaction of one nanomaterial with biomolecules. Here, one can not only exploit variations in the nanomaterial structure or surface, but we need to exploit more the potential of protein engineering. The recombinant preparation of proteins and mutants of the native molecule allows much better to elucidate which part of the protein surface is responsible for the surface interaction. However, also with mutants, care has to be taken that the modified protein has still the same 3D structure as the native biomolecule—a fact which is not always controlled in mutational studies.

For several nanomaterials, different shapes can be achieved by innovative preparation protocols. This is on the one hand a large “playground” to work on, and on the other hand, we do not understand which structural parameters are important for a productive interaction with a given redox biomolecule.

Thus, we need more collaborations between people from biochemical research, materials chemistry and electrochemical sciences. Here, biochemistry is not only acting as servant for electrochemistry, but one can study functional properties by electrochemistry, and thus, new information can be gained about biomolecules. Thus, electrochemistry will also develop as a tool for studying biochemical systems.

A special group of materials are polymers which have been used from early days of biosensor research as an immobilisation matrix [22]. Another role of polymers can be, however, exemplified with many enzymes and redox polymers with embedded redox centres. Here, studies show that biomolecular interaction with the polymer is influenced by the ligand shell of the metal centers and the redox potential but also the structural flexibility—mainly tested by variations in the linker length between the metal complex and the polymer backbone [23,24,25]. This allows the construction of defined signal chains from analyte molecules converted at the enzyme towards a current flow at the electrode. For other groups of polymers, we have much less knowledge. For example, conducting polymers seem also to be very attractive materials on electrodes since they can transport electrons through the polymeric chains [26,27,28,29]. However, only few systems with clear electron exchange between a biocatalyst and a conducting polymer have been demonstrated. The conditions for an effective reaction between an enzyme and a conducting polymer cannot simply be foreseen yet.

Polymers seem also valuable in combining different biomolecules on one electrode and thus, creating supramolecular structures. This originates from the idea to combine various features of different molecules for a new functionality of the whole system. For the arrangement of molecules, bioaffinity binding, covalent coupling, electrostatic layer-by-layer deposition or entrapment systems with different biomolecules and redox polymers can be used [30,31,32,33,34]. Here, one can expect significant progress since the work of enzymes in a cooperative, sequential, recycling or competitive mode follows very much biological examples. The systematic arrangement of biomolecules allows the creation of defined pathways with low diffusional distances and high conversion efficiencies. We are only at the beginning of development with some recent examples coupling enzyme reactions to photoactive protein complexes [35] or switching between different enzymes [36].

This points to another actual research direction: the combination of light-induced charge carrier generation and biocatalysis [37,38,39]. One could argue on the complexity of such systems, but when light activation is applied, electrons from oxidation processes can be collected at much lower electrode potential than the redox potential of the enzyme. And for reduction processes, electrons can be supplied at much higher potential. This is interesting from the energetic point of view, and thus, development will grow in this area. In addition, the light can be used as tool for multiplexing.

Another field of electrochemical research has seen some dramatic development in the last decade. It is based on the coupling of even more complex biological structures to electrodes—whole cells. Here, one needs to realise that only little can be transferred from isolated biomolecules to living structures on the surface. Application seems attractive in wastewater treatments and thus bioenergetics, but also in sensing—particularly for environmentally relevant substances [40,41,42,43]. The living character has to be taken in consideration by conditions and the supply of nutrients, but it also allows much better stability of a biofilm on an electrode compared with an enzyme layer. However, there is a lack in understanding of such systems, and thus, again collaboration of experts from different fields such as microbiology, bioprocess technology, biochemistry and electrochemistry is necessary.

The deepening of understanding biomolecular interactions with surfaces and materials will also help to come to more systems which will find application in an everyday life situation. Presently, this can be mainly seen in simple detection systems which can be coupled to digital read out units and which are directed to biomarkers, toxins, but also viruses and bacteria. But there is also room for other fields such as synthesis of special chemicals and energy conversion.