A number of medications for short-term and long-term use have been linked to an increased risk for keratinocyte carcinoma (KC). Immunosuppressive medications are associated with an increased risk for KC and melanoma due to reduction of antitumor immune surveillance, and some immunosuppressive agents directly impact DNA replication and repair. Clinical and epidemiologic studies have shown an increased risk for KC in users of photosensitizing medications. Additional mechanisms include drug-induced modulation of DNA damage repair, enhancement of keratinocyte proliferation, and direct carcinogenic effect. Alternatively, some medications potentially decrease KC risk. This article reviews the literature on medications associated with KC risk.