Histone deacetylase inhibitors (HDAC-Is) are agents that have demonstrated anticancer activity in vivo and in vitro, leading to clinical trials evaluating their efficacy in multiple cancer types. Only two HDAC-Is are currently approved by the U.S. Food and Drug Administration, vorinostat and romidepsin, both with indications for cutaneous T-cell lymphoma. Romidepsin has an additional approval in peripheral T-cell lymphoma. Promising clinical trial results in other cancer types will likely lead to expanded use of these and other HDAC-Is. To provide care for patients receiving these agents, oncology nurses should be knowledgeable about the emerging role of HDAC-Is. This article reviews the mechanism of action of HDAC-Is, currently approved therapies, and nursing management of cutaneous T-cell lymphoma.