Palmoplantar psoriasis (PP) and palmoplantar pustulosis (PPP) are diseases affecting the hands and/or feet that can cause marked physical discomfort and functional disability. The tumor necrosis factor-alpha antagonists adalimumab, etanercept, and infliximab, the interleukin (IL)-17A inhibitors ixekizumab and secukinumab, and the IL-23 or IL-12/IL-23 inhibitors guselkumab and ustekinumab have been well studied for the treatment of moderate to severe plaque psoriasis. Less is known about the efficacy and safety of these agents for the treatment of PP (hyperkeratotic and pustular forms) and PPP. The aim of this review was to investigate the efficacy of biologic therapy for the treatment of hyperkeratotic PP, pustular PP, and PPP.A systematic search of the medical electronic databases (Medline, Embase, and Cochrane Library) was conducted to identify studies or case reports which both used biologic therapy for the treatment of hyperkeratotic PP, pustular PP, and PPP and reported treatment outcomes.The systematic search identified 579 published articles, of which 44 were included in the analysis. Seven of the articles involved randomized placebo-controlled trials, two were open label trials, and the remaining were cohort studies, case series, or case reports. In the randomized controlled trials on the treatment of hyperkeratotic PP, adalimumab, guselkumab, infliximab, ixekizumab, and secukinumab each demonstrated superiority to placebo at 16, 16, 14, 12, and 12 or 16 weeks, respectively (p < 0.05). For the treatment of pustular PP, ustekinumab 45 mg was not superior to placebo at 12 and 16 weeks, respectively (p > 0.05), although an open label study demonstrated that four of five patients on a therapeutic regimen of ustekinumab 90 mg achieved clinical clearance at 16 weeks. For the treatment of PPP, etanercept and ustekinumab 45 mg were not superior to placebo at 12 and 16 weeks, respectively (p > 0.05). A combined analysis of studies for hyperkeratotic PP demonstrated that 94.7%, 90.0%, 82.5%, 89.1%, and 86.7% of patients experienced an improvement of at least 50% upon treatment with adalimumab, guselkumab, ixekizumab, secukinumab, and ustekinumab, respectively. In a combined analysis of case reports examining PPP, infliximab showed the greatest efficacy at 100.0% clinical improvement of patients from case reports, followed by ustekinumab at 58.8% clinical improvement. Few serious adverse events were reported, but several were reported in patients treated with infliximab or secukinumab.Biologic therapy is effective and well-tolerated for the treatment of hyperkeratotic PP, but less data are available on the treatment of pustular PP or PPP. Adalimumab, guselkumab, ixekizumab, secukinumab, and ustekinumab all showed > 80% efficacy for the treatment of hyperkeratotic PP, while infliximab and ustekinumab showed moderate efficacy for the treatment of pustular PP, and infliximab was the most efficacious treatment for PPP.