5α-Reductase inhibitors (5-ARIs) are widely prescribed for treatment of lower urinary tract symptoms (LUTS) due to benign prostatic obstruction (BPO) and of androgenic alopecia (AA). In 2017, the Post-Finasteride Syndrome Foundation raised concerns about the potential risks of depression and suicide associated with 5-ARIs. Although the US Food and Drug Administration stated that their petition did “not provide reasonable evidence” of such an association, the issue prompted inclusion of depression as an adverse effect on the label for finasteride. Several studies with controversial findings regarding 5-ARI exposure have been published over a number of years. In a pharmacovigilance case versus non-case study using data from VigiBase (World Health Organization global database of individual case safety reports), Nguyen et al [1] found higher rates of suicidality among young patients (aged <45 yr), but not older patients. In a large Swedish register-based cohort study, Garcia-Argibay et al [2] found a 1.6-fold increase in the risk of depression for patients exposed to 5-ARIs and a 2.2-fold increase in the risk of suicide when 5-ARIs were combined with α-blockers. Notably, for patients exposed to finasteride or dutasteride alone, no significant association with the risk of suicide was found [2]. To investigate the association between 5-ARI use and the risk of depression or suicide, we conducted a systematic review of the literature and performed a meta-analysis of relevant studies.