Histone deacetylase inhibitors (HDACi) are a new class of antineoplastic agents with demonstrable preclinical antitumor activity in both in vitro and in vivo studies in a wide range of malignancies. Based on these preclinical findings, in recent years HDACi have undergone a rapid phase of clinical development with many HDACi entering Phase I-III clinical trials, both as single agents and in combination with other therapies. Favorable clinical responses have been demonstrated in cutaneous T-cell lymphoma with emerging evidence of clinical activity in other types of lymphoma and, to date, a good toxicity profile. Solid tumor responses to single agent and combination therapies have also been reported, paving the way for larger studies in this field. In this review we discuss the recent advances in the clinical development of HDACi and their current therapeutic role in lymphoma and solid malignancies.