This article discusses the advances in targeting histone deacetylase (HDAC) for the treatment of solid tumors. HDACs play a critical role in the pathobiology of various malignancies, and HDAC inhibitors (HDACis) have been developed as potential therapeutic agents. Preclinical studies have shown antitumor effects of HDACis, either as monotherapy or in combination treatments. Clinical trials have been conducted to evaluate the efficacy of selective and pan-HDACis in solid tumors. The article highlights both successful and unsuccessful clinical trials, analyzing factors such as toxicological side effects, tumor heterogeneity, and off-target effects that may have contributed to less-than-expected results. Despite these challenges, the article suggests that advancements in HDACi research and combination therapies could lead to improved treatment outcomes for solid tumors. The functions and classification of HDACs are discussed, along with their role in tumor progression. The article also provides an overview of HDAC inhibitors, their mechanisms of action, and their potential in combination therapies. Preclinical evidence of HDACis in monotherapy and combination treatments is presented, highlighting their efficacy in various tumor types. The article also discusses the use of HDACis in sensitizing tumors to chemotherapy, targeted therapy, radiotherapy, immunotherapy, and endocrine therapy. Finally, the article summarizes the clinical trials of HDACis in solid tumors, highlighting both promising results and challenges encountered. Overall, the article emphasizes the potential of HDACis in the treatment of solid tumors and the need for further research and development in this area.This article discusses the advances in targeting histone deacetylase (HDAC) for the treatment of solid tumors. HDACs play a critical role in the pathobiology of various malignancies, and HDAC inhibitors (HDACis) have been developed as potential therapeutic agents. Preclinical studies have shown antitumor effects of HDACis, either as monotherapy or in combination treatments. Clinical trials have been conducted to evaluate the efficacy of selective and pan-HDACis in solid tumors. The article highlights both successful and unsuccessful clinical trials, analyzing factors such as toxicological side effects, tumor heterogeneity, and off-target effects that may have contributed to less-than-expected results. Despite these challenges, the article suggests that advancements in HDACi research and combination therapies could lead to improved treatment outcomes for solid tumors. The functions and classification of HDACs are discussed, along with their role in tumor progression. The article also provides an overview of HDAC inhibitors, their mechanisms of action, and their potential in combination therapies. Preclinical evidence of HDACis in monotherapy and combination treatments is presented, highlighting their efficacy in various tumor types. The article also discusses the use of HDACis in sensitizing tumors to chemotherapy, targeted therapy, radiotherapy, immunotherapy, and endocrine therapy. Finally, the article summarizes the clinical trials of HDACis in solid tumors, highlighting both promising results and challenges encountered. Overall, the article emphasizes the potential of HDACis in the treatment of solid tumors and the need for further research and development in this area.