HDAC inhibitors (HDACis) are a class of drugs that target histone deacetylases (HDACs), enzymes involved in epigenetic regulation. Dysregulation of HDACs is associated with various cancers, and HDACis have shown promise as anticancer agents. Two HDACis, vorinostat and romidepsin, have been FDA-approved for the treatment of refractory cutaneous T-cell lymphoma. Other HDACis are currently under clinical development. HDACs are classified into several families, with class I, II, and IV being the most studied. Class III HDACs, or sirtuins, are not typically targeted by conventional HDACis. HDACs regulate gene expression by modifying histones, and their dysregulation can lead to cancer progression. Overexpression of certain HDACs is linked to poor prognosis in various cancers, while others may have tumor suppressor roles. HDAC inhibition can induce apoptosis, growth arrest, and differentiation in cancer cells, and may also enhance metastasis. The mechanisms of HDACi action are complex and depend on the specific HDACs targeted and the cellular context. HDACis are being investigated for their potential in treating various cancers, including hematological malignancies such as Hodgkin lymphoma, multiple myeloma, and AML. However, their efficacy in solid tumors has been limited. New HDACis are being developed with improved specificity and potency. Class I HDACs, such as HDAC1, -2, and -3, are frequently overexpressed in tumors and are important targets. HDAC8, while less studied, may play a role in solid tumors. Class II HDACs, particularly HDAC4, -5, -7, and -9, are also being explored for their potential in cancer therapy. Hybrid molecules that target both HDACs and other oncogenic proteins are being developed to improve the specificity and efficacy of HDACis. Clinical trials are ongoing to evaluate the safety and effectiveness of these new agents. While HDACis have shown promise, challenges remain in optimizing their use and minimizing toxicity. Further research is needed to fully understand the roles of HDACs in cancer and to develop more effective and targeted therapies.HDAC inhibitors (HDACis) are a class of drugs that target histone deacetylases (HDACs), enzymes involved in epigenetic regulation. Dysregulation of HDACs is associated with various cancers, and HDACis have shown promise as anticancer agents. Two HDACis, vorinostat and romidepsin, have been FDA-approved for the treatment of refractory cutaneous T-cell lymphoma. Other HDACis are currently under clinical development. HDACs are classified into several families, with class I, II, and IV being the most studied. Class III HDACs, or sirtuins, are not typically targeted by conventional HDACis. HDACs regulate gene expression by modifying histones, and their dysregulation can lead to cancer progression. Overexpression of certain HDACs is linked to poor prognosis in various cancers, while others may have tumor suppressor roles. HDAC inhibition can induce apoptosis, growth arrest, and differentiation in cancer cells, and may also enhance metastasis. The mechanisms of HDACi action are complex and depend on the specific HDACs targeted and the cellular context. HDACis are being investigated for their potential in treating various cancers, including hematological malignancies such as Hodgkin lymphoma, multiple myeloma, and AML. However, their efficacy in solid tumors has been limited. New HDACis are being developed with improved specificity and potency. Class I HDACs, such as HDAC1, -2, and -3, are frequently overexpressed in tumors and are important targets. HDAC8, while less studied, may play a role in solid tumors. Class II HDACs, particularly HDAC4, -5, -7, and -9, are also being explored for their potential in cancer therapy. Hybrid molecules that target both HDACs and other oncogenic proteins are being developed to improve the specificity and efficacy of HDACis. Clinical trials are ongoing to evaluate the safety and effectiveness of these new agents. While HDACis have shown promise, challenges remain in optimizing their use and minimizing toxicity. Further research is needed to fully understand the roles of HDACs in cancer and to develop more effective and targeted therapies.