The evidence for vitamin B₆ supplementation as a treatment for depression was evaluated. Medline, PsychInfo, Amed and Cochrane Controlled Trials Register were searched from database inception through to September 2001. All RCTs, CCTs, intervention studies, case-control studies, reviews and case reports examining the evidence behind vitamin B₆ in depression among humans were included. No limits were placed for demographics or co-morbidities. Only English language papers were abstracted and assessed for trial quality. Two abstractors independently evaluated each study, then reconciled findings. As data were available, between group treatment effect size was noted or, as needed, calculated. When studies reported outcome effects using multiple measures, data were abstracted to permit the greatest possible comparisons among papers. Ten articles met inclusion criteria: three reviews, one case report, five RCTs and one intervention study. There was no common outcome measure among all studies, eliminating the opportunity for direct comparison of effect sizes. As an alternative means of comparison, effects were plotted as they related to the null hypothesis. A meaningful treatment effect of vitamin B₆ for depression in general was not apparent. However, examination of papers addressing depression in pre-menopausal women only revealed a consistent message about the value of using vitamin B₆ supplementation.