Rituximab was the first monoclonal antibody used for the treatment of a malignancy. In the 22 years since initial approval, it has become a vital component of therapy for a multitude of B-cell malignancies. Within the last several years, however, there has been a robust development of novel agents targeting CD20, including second generation anti-CD20 antibodies, biosimilar antibodies, and subcutaneous formulations that have been approved. The era of passive immunotherapy is now yielding to therapeutic approaches that actively engage the immune system. Emerging approaches leverage immunomodulatory drugs or novel checkpoint inhibitors to enhance CD20 therapy. Recent data sets on bispecific CD3/CD20 antibodies demonstrate exciting early findings, and CD20-directed chimeric antigen receptor T-cell therapies are now entering clinical trials. Anti-CD20 therapies are a vital component of the treatment of B-cell malignancies, and there is a dynamic therapeutic environment with multiple new data sets reviewed here.