Cancer is the cause of nearly 10 million deaths per year, making it one of humanity's most significant disease burdens, particularly in western societies. It arises from a variety of factors, including genetic mutations and epigenetic alterations, the latter involving chromatin modifications without changes to the DNA sequence. Chromatin remodeling, like ε-lysine acetylation of histones, is tightly regulated, as it is responsible for modulation of transcription, DNA repair, replication, and condensation. To reverse the acetylation, histone deacetylases (HDACs) hydrolyze the amide bond, restoring the positive charge of the lysine and resulting in a more compact chromatin. HDACs can be distinguished into four classes: Class I (HDAC1-3 and 8), class IIa (HDAC4, 5, 7 and 9), class IIb (HDAC6 and 10) and class IV (HDAC11) are zinc-dependent deacylases. Depending on the isoform, they are primarily localized in the nucleus or in the cytoplasm and some contribute to multi-protein complexes. In addition, HDACs act on multiple substrates beyond histones and are involved in the hydrolysis of more than just acetyl groups. The up-regulation and high expression of different HDAC isoforms are associated with poor prognosis in cancers such as multiple myeloma and acute myeloid leukemia. Therefore, HDAC inhibition is a promising strategy for tumor therapy. Numerous studies have demonstrated that HDAC inhibitors (HDACi) reduce angiogenesis, cell migration, proliferation, and resistance to chemotherapy. Furthermore, inhibition of HDACs promotes apoptosis and enhances cell differentiation. U.S. Food and Drug Administration (FDA) or European Medicines Agency (EMA) approved HDACi, such as vorinostat, belinostat, and romidepsin, for the treatment of T-cell lymphoma, panobinostat for the treatment of multiple myeloma, and givinostat for treating Duchenne muscular dystrophy.