Abstract Venetoclax (VEN), a small-molecule inhibitor of B cell leukemia/lymphoma-2, is now FDA approved (November 2018) for use in acute myeloid leukemia (AML), specific to newly diagnosed elderly or unfit patients, in combination with a hypomethylating agent (HMA; including azacitidine or decitabine) or low-dose cytarabine. A recent phase-3 study compared VEN combined with either azacitidine or placebo, in the aforementioned study population; the complete remission (CR) and CR with incomplete count recovery (CRi) rates were 28.3% and 66.4%, respectively, and an improvement in overall survival was also demonstrated. VEN-based chemotherapy has also shown activity in relapsed/refractory AML (CR/CRi rates of 33–46%), high-risk myelodysplastic syndromes (CR 39% in treatment naïve, 5–14% in HMA failure), and blast-phase myeloproliferative neoplasm (CR 25%); in all instances, an additional fraction of patients met less stringent criteria for overall response. Regardless, venetoclax-induced remissions were often short-lived (less than a year) but long enough to allow some patients transition to allogeneic stem cell transplant. Herein, we review the current literature on the use of VEN-based combination therapy in both acute and chronic myeloid malignancies and also provide an outline of procedures we follow at our institution for drug administration, monitoring of adverse events and dose adjustments.