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Acute myeloid leukemia (AML) is a highly heterogeneous disease. This heterogeneity often leads to treatment failure or unsustainable efficacy, and high relapse rates as well as short progression-free survival (PFS) are closely associated with poor prognosis. Cyclin-dependent kinases (CDKs) play a central role in cell cycle regulation, transcription regulation, and metabolic processes, and their aberrant expression or dysfunction is considered as one of the key drivers of AML progression. Recent studies have increasingly focused on CDK inhibitors, aiming to address drug resistance and improve prognosis. Although some CDK inhibitors have shown promising anti-AML potential, challenges such as off-target effects and systemic toxicity remain daunting. This review systematically summarized the research progress of CDK inhibitors in the treatment of AML, with a particular focus on the results of preclinical studies and clinical trials targeting CDKs in AML, such as CDK2, CDK4/6, CDK7, and CDK9. In addition, the limitations of current therapeutic applications of CDK inhibitors were discussed, and potential strategies to overcome these challenges were explored, aiming to provide a reference for optimizing AML treatment regimens.