Histone Deacetylase Inhibitors (HDACi) inhibits deacetylases of histones and nonhistones. As such it has potential widespread biological effects. However, cancer cells are preferentially affected than normal cells making it a useful targeted therapy in cancer. HDACi has therapeutic effects in hematological malignancies like acute myeloid leukemia and multiple myeloma. The molecular effect is dependent on the cancer type, the specific class of histone deacetylase, and the chemical structure of the HDACi. This chapter focuses on the basics of HDAC classification and the specific molecular effects in multiple myeloma.