There are sex differences in the prevalence and presentation of many psychiatric disorders. Various trends in symptomatology have emerged that are thought to be linked to periods of hormonal fluctuations such as with menses, pregnancy or menopause. With data from animal and human studies, it has become clear that there is an important interplay between the serotonergic system and gonadal hormones. The majority of the research to date has focused on the influence that estrogen has within the CNS and, in particular, how it leads to an overall increase in serotonin synthesis and availability. In reviewing this female-specific topic we hope to raise awareness to sex/gender differences in psychopathology, help identify at-risk populations and consider development of new treatment options. Future research will also need to consider the influence that progesterone and oxytocin may have on sex-specific psychopathology as well as incorporate neuroimaging and consider the influence of hormones on the serotonergic system at a genetic level.