A number of new, biologic targeted therapies have been developed for the treatment of lymphoid malignancies. These include anti-CD20 monoclonal antibodies designed with greater binding affinities and different mechanisms of action profiles compared with rituximab. Other extracellular antigens on B cells and T cells are also being targeted. Monoclonal antibodies have been conjugated to radioisotopes and cellular toxins. In addition, several exciting new small-molecule kinase inhibitors are in development that target intracellular pathways that contribute to the pathogenesis of these diseases. Drugs that affect the tumor microenvironment are also under investigation. The advantage of these targeted agents compared with standard chemotherapy is greater tumor specificity, a more favorable toxicity profile, and, when combined with scientific rationale, and in the appropriate setting, perhaps a better long-term outcome.