Premature ejaculation (PE) is a common condition associated with significant adverse effects on the sexual and overall quality of life of men with this condition. Behavioral therapies, such as the “squeeze” and “stop–start” techniques, and psychotherapy, have been the mainstay of PE management for many years. However, evidence of their short-term efficacy is limited while support for their long-term benefit is lacking. There are currently no medications licensed specifically for the treatment of PE. This paucity of pharmacological treatment may, in turn, contribute to the absence of systematic procedures for the identification, evaluation, and treatment of PE patients. Current “off-label” pharmacotherapeutic approaches include topical anesthetics, phosphodiesterase-5 inhibitors, and serotonin reuptake inhibitors. Of these, the serotonin reuptake inhibitors show the greatest efficacy and an increasing body of evidence is illuminating their mode of action. Nevertheless, all current “off-label” pharmacotherapeutic approaches fall short of the ideal therapy for PE. In the absence of a cure, such a treatment should be tolerable, inconspicuously used, effective from first dose, rapid in onset of action, and available as a prn-dosing regimen. It is anticipated that agents in development for the specific indication of PE will come closer to this ideal than existing pharmacotherapeutic approaches.