The management of psoriatic disease in the human immunodeficiency virus (HIV)-positive population is challenging. The clinical course often is progressive and refractory; therefore, first- and second-line therapies including topical agents, phototherapy, and oral retinoids often are inadequate. Most other currently available systemic therapies for psoriatic disease are immunosuppressive, which poses a distinct clinical challenge. A comprehensive systematic review of the literature via a PubMed search of articles indexed for MEDLINE using the terms psoriasis and HIV and psoriatic arthritis and HIV combined with several systemic immunosuppressive agents yielded a total of 25 reported cases of systemic immunosuppressive therapies used to treat psoriatic disease in HIV-positive patients including methotrexate, cyclosporine, etanercept, adalimumab, infliximab, and ustekinumab. The limited data suggest that biologic therapies may be effective for cases of psoriasis recalcitrant to other systemic agents and may have a positive effect on CD4 and viral counts when used in combination with highly active antiretroviral therapy (HAART); however, further studies are needed.