Society faces multiple challenges in this millennium and education should promote skills that allow students and teachers to face them. Students will have to be prepared for jobs that have not yet been created, for technologies that have not yet been invented, to solve problems that have no yet been anticipated. As educators will be a shared responsibility to take advantage of the opportunities and find solutions. In this context, international organizations linked to educational change are rethinking the role of the current education. One initiative is the creation of frameworks to promote and develop skills for the 21st century which are defined as a set of skills necessary to interact in today’s world, mainly in study and employment, where the management of technology is crucial. In Chile, initiatives in this area are being foreshadowed and it is necessary to define a reference framework that complement this process. The aims of this paper is to propose a frame of reference of skills for the 21st century that synthesizes the diversity of referents to have a useful referent to guide educational innovation processes in our Latin American context. Based on a comparative methodology, it was applied a descriptive-comparative analysis of frameworks formulated by international organizations that promote these skills. Theoretical analysis results show concordance in five categories: Cognitive, Social, Emotional, Information and Communication Technologies (ICT), and Curricular Contents for the 21st century. With this background, we are able to present a referential framework maintaining the five categories, and adding 38 essential skills.