Waldenstr?m macroglobulinemia (WM) is a rare indolent lymphoplasmacytic lymphoma. Bruton’s tyrosine kinase (BTK) plays a key role in the signaling pathway of WM, which has changed the way of treatment of WM. As a first-generation BTK inhibitor, ibrutinib is an early-stage treatment and a salvage treatment that can control toxicity characteristics. However, in order to overcome the resistance of the first-generation BTK inhibitors, reduce the adverse reactions caused by off-target effects, and improve the efficacy, the research and development of new BTK inhibitors has become a hot topic. This article discusses the clinical studies of the first generation and new BTK inhibitors for WM, aiming to provide a certain basis for the more rational application of BTK inhibitors in WM.