The histone tails of histone octamers play an intricate role in transcription, and aid the histone interaction and binding with the negatively charged DNA phosphate backbone. Histone acetyl transferases and histone deacetylase inhibitors respectively accomplish acetylation and deacetylation of the lysine residue of the histone tail. Vorinostat is the first and only histone deacetylase inhibitor with activity in cutaneous T-cell lymphoma (CTCL) approved by the US Food and Drug Administration (FDA). CTCL refers to a diverse group of disorders, including the most common mycosis fungoides, and the less common but more aggressive Sézary syndrome. The exact mechanism of action of vorinostat is unknown; however, it involves the up- and down-regulation of multiple cell cycle pathways. Vorinostat exhibits better efficacy in hematologic malignancies than in solid tumors. Numerous clinical trials involving vorinostat alone and in combination with other agents in multiple malignancies and solid tumors have reported patient clinical benefit. Overall, the adverse-effect profile of vorinostat is very favorable, and the product is a good candidate for single-agent use as well as for combination therapy.