Historically, four periods can be distinguished in the approach to and treatment of lifelong premature ejaculation. Although drug treatment has been an option for many decades, psychotherapy prevailed as the first choice of treatment. However, the application of the principles of evidence-based medicine shows that there is little evidence to support the psychological approach and behavioural treatment. In contrast, controlled trials with selective serotonin reuptake inhibitors, clomipramine and anaesthetic ointments have repeatedly shown the efficacy of both daily and ‘as-needed’ drug treatment to delay ejaculation. Currently, an evidence-based approach is gradually replacing the authority-based psychological attitude that characterized the view of premature ejaculation. Based on psychopharmacological studies there is evidence that premature ejaculation is related to a diminished serotonergic neurotransmission, and 5-HT2C or 5-HT1A receptor disturbances. Moreover, animal studies show the presence of a distinct ejaculation-related neural circuit in the central nervous system; its role in premature ejaculation remains to be elucidated.