Premature ejaculation (PE), the most common sexual dysfunctions in men, is characterized by loss or absence of ejaculatory control. PE can be classified as either a lifelong or acquired condition. Although the prevalence of lifelong PE is rather low in the general male population, recent studies demonstrated that the patients who seek treatment for their rapid ejaculation mostly report lifelong PE. Although no drug for PE has been approved by regulatory bodies, chronic selective serotonin reuptake inhibitors (SSRIs) proved to be effective in treating lifelong PE. Despite the rising use and known effects of antidepressants on ejaculation, only a few reports have evaluated the impact of these drugs on the male fertility. Thus, the aim of this review is to evaluate the efficacy and adverse effects of SSRIs on semen parameters of patients with lifelong PE as well as to assess the safety of this treatment among sexually active couples who desire to have a child.