Venetoclax is a selective inhibitor of BCL-2, which is well tolerated in acute myeloid leukemia (AML) patients. In recent years, the use of Venetoclax has become more common, and most AML patients have responded well to Venetoclax-based combination regimens. Clinically, Venetoclax is generally used in combination with low-dose cytarabine or demethylating drugs, and both have achieved a higher remission rate than single-agent therapy. and the patient is well tolerated. Nowadays, targeted therapy drugs are developing rapidly. The clinical trials of Venetoclax combined with various targeted drugs are underway, with the hope to guide the clinical treatment of AML. However, the curative effect of Venetoclax is not long-lasting, and it is easy to develop resistance and relapse. The resistance mechanism of Venetoclax is complicated and has not been fully clarified. Therefore, during the application of Venetoclax, attention should be paid to the emergence of drug resistance.