Recently, it has been suggested that premature ejaculation (PE) might be associated with perturbations in serotonergic 5-hydroxytryptamine (5-HT) neurotransmission. It has been proposed that PE may be caused by decreased central serotonergic signaling, hyposensitivity of the 5-HT2C receptor, or hypersensitivity of the 5-HT1A receptor, all of which have been shown to decrease ejaculatory latency time in animal model systems. PE is a common problem, which may be associated with considerable anxiety, frustration, and negative impact on affected men and their sexual partners. No pharmaceutical agents have been approved for this indication. However, therapies that target 5-HT neurotransmission, such as selective serotonin reuptake inhibitor (SSRI) anti-depressants, have been used in this setting with varying efficacy and tolerability.