Despite the development of novel treatments, multiple myeloma (MM) and light-chain (AL) amyloidosis remain incurable diseases. BCL2 inhibitors are a class of drugs under development for plasma cell disorders, with strong data supporting their use, particularly in patients with MM and AL amyloidosis harbouring the t(11
14). Venetoclax, the most extensively studied BCL2-specific inhibitor, was initially designed and evaluated for other malignant blood disorders. However, it has since shown promising efficacy in both randomized and real-world studies for MM and AL amyloidosis, either as a monotherapy or in combination with other agents. Nonetheless, toxicity concerns have been raised, underscoring the need for careful patient selection and precise dose optimization. Additionally, other BCL2-targeting drugs are under investigation in preclinical and clinical studies. This review focuses on the current role of BCL2 inhibitors in the treatment landscape of MM and AL amyloidosis.