Monoclonal antibodies are expanding the therapeutic options for patients with B-cell lymphoma. Despite the antitumor activity of rituximab alone or in combination with systemic chemotherapy against various subtypes of B-cell lymphomas, a significant number of patients relapse or do not respond to initial therapy, stressing the need to identify novel molecular targets. CD80 is a surface glycoprotein and a member of the B7 family of costimulatory molecules. CD80 antigen is expressed in antigen-presenting cells, normal B cells, and various subtypes of B-cell lymphomas. Moreover, CD80 is an important regulator of T-cell activation. In addition, in vitro binding of CD80 by specific monoclonal antibodies (MoAbs) results in growth inhibition and apoptosis of normal and malignant B cells. Galiximab is a primatized MoAb targeting CD80. Preclinical studies had shown significant antitumor activity as a single agent or in combination with rituximab against various B-cell lymphoma cell lines in vitro and in vivo. An initial phase I/II study with galiximab as a single agent in patients with relapsed B-cell lymphoma demonstrated its safety and antitumor activity and had provided a framework for future studies. Interestingly, and in contrast with what had been observed with other biologic agents, the time to best response for the responding patients was delayed, suggesting an alternative mechanism of action other than the traditional antibody-dependent cellular cytotoxicity, apoptosis, and complement-mediated cytotoxicity. Ongoing and future studies are warranted to further evaluate the therapeutic role of galiximab in the treatment of patients with B-cell lymphomas in combination with rituximab or systemic chemotherapy.