The non-Hodgkins lymphomas are a diverse groups of lymphoid neoplasms that collectively rank fifth in cancer incidence and mortality. Conventional treatment for patients with newly-diagnosed non-Hodgkins lymphoma (NHL) includes radiation or chemotherapy. In addition, those with asymptomatic low-grade disease may follow a “watch and wait” approach. Single agent oral alkylating therapy and CVP (cyclophosphamide, vincristine, and prednisone) have become a mainstay of treatment for low-grade NHL. High intensity chemotherapy consisting of the anthracycline, doxorubicin along with cyclophosphamide, vincristine and prednisone (CHOP) is offered as standard treatment for intermediate-grade NHL. Following relapse, salvage therapy rarely results in long-term survival in patients with low-grade NHL. Up to 50% of patients die within five years of first relapse. For patients with intermediate-grade NHL who relapse after or do not respond to first-line treatment, a range of combination regimens can be offered, composed of non-cross resistant drugs not typically used during first-line treatment. However, less than half of patients with intermediate-grade disease achieve prolonged disease-free survival. With todays conventional treatments, cure is only a possibility for a minority of patients with intermediate-grade disease and a limited group of patients with indolent NHL who are diagnosed at early stages. Novel approaches to treatment are therefore needed. Monoclonal antibodies may fulfill this need, administered either as single agents or in conjunction with conventional cytotoxic approaches. The task now lies in determining how best to use this new modality, with the hope of bringing a cure to a greater number of patients.