The object of this comprehensive review is to provide the clinician with an overview of the factors involved in everyday clinical practice when sexuality is an element of a major depressive episode in monopolar patients. In our opinion, functional recovery in patients with monopolar depressive disorder includes achieving healthy sexuality. This requires the clinician to bear this issue in mind, consider it in his/her assessment, be familiar with these bidirectional relations and involve these variables in his choice of pharmacological treatment. We also consider it important to include sexuality in the profiling process in order to select the most effective antidepressant treatment. We analyse the most frequent antidepressant strategies and the pharmacological groups most used in this area, consistent with what is known today about this diad and how it relates with antidepressant action mechanisms.