Anti-tumor necrosis factor therapy has shown remarkable safety and efficacy in the treatment of many autoimmune and inflammatory disorders, although limited published data exists regarding these treatments in patients with concomitant human immunodeficiency virus and/or acquired immune deficiency syndrome. The use of tumor necrosis factor inhibition is associated with an increased risk of severe infections, including tuberculosis and risk of worsening hepatitis B virus, but its effect on viral infections is conflicting. Currently, package inserts for the three anti-tumor necrosis factor medications (infliximab, etanercept, and adalimumab) affirm that caution should be exercised when considering their use in patients with chronic infection or a history of recurrent infection, as clinical trials for these medications have historically excluded patients with chronic viral infections. With the increasing prevalence of chronic viral infections in patients who are candidates for anti-tumor necrosis factor therapy, there is reason for additional research to assess the safety, efficacy, and potential role of tumor necrosis factor inhibition in this population. This article is an up-to-date review of the emerging use of biologic therapies in patients infected with the human immunodeficiency virus and concurrent psoriatic or rheumatological disease.