The therapeutic options for B-cell non-Hodgkin's lymphoma (NHL) have dramatically expanded with the advent of immune-based treatments. The monoclonal antibody anti- CD20 rituximab represents the best example of these advances and has quickly become incorporated into the therapeutic armamentarium for this hematological disease. In addition, other antibodies are eventually becoming part of treatment approaches to NHL. Furthermore, the role of therapeutic vaccines continues to be an important ongoing research question. Despite this success, several questions on how to optimize the use of monoclonal antibodies in NHL remain open since the best administration schedules, as well as the optimal duration of immunotherapy still have to be determined. Finally the development of resistance to treatment remains the main limit of this innovative approach, necessitating the development of strategies to circumvent resistance itself. This review will summarize the state of the art of antibody-based immunotherapy of NHL and discuss prospective approaches to improve the benefit of these treatments in patients.