Major depressive disorder (MDD) is one of the most common mental disorders, with a lifetime prevalence of approximately 13% in Europe. Although the primary symptom of MDD is depressed mood and a loss of interest or pleasure in everyday life, patients with MDD often present with a variety of other symptoms, such as sleep disturbances, fatigue, anxiety and somatic complaints. Antidepressant drugs are frequently used as first-line therapy for MDD. Bupropion is a second-generation antidepressant drug that inhibits reuptake of the neurotransmitters dopamine and norepinephrine, and has no direct serotonergic effects, a unique property among antidepressants. This article highlights the use of bupropion in the treatment of three patients with varying presentations of MDD, including as combination therapy in a patient refractory to treatment with a selective serotonin reuptake inhibitor, monotherapy in a patient with somatic symptoms of depression and loss of libido, and in a patient complaining of anxiety as a symptom of MDD. Bupropion treatment was successful in all patients, resulting in remission of symptoms and the patients returning to their normal lives.