Non-Hodgkin's lymphoma (NHL) includes multiple neoplastic disorders of the lymphoid system with overlapping features. NHL is characterized by a monoclonal expansion of lymphoid cells, excluding those from primitive precursors that give rise to acute lymphoblastic leukemia and plasma cells that give rise to multiple myeloma. The malignant cell for most lymphomas can be traced to a specific stage in lymphoid maturation; lymphomas most commonly derive from mature B cells of germinal center origin. The cell of origin and stage of maturation arrest are important for understanding pathobiology and the identification of potential therapeutic targets. The clinical presentation is variable and depends on a number of factors, including histology, patient age, and immune status. NHL typically presents with lymphadenopathy that can range from relatively asymptomatic to causing organ compromise such as ureteral obstruction or spinal cord compression. Patients may have constitutional manifestations due to inflammatory molecules and a variety of other cytokines and chemokines that are produced by the lymphoma cells and/or host tissues. Without effective intervention, death is usually invariable. Current treatments have a powerful effect on the natural history of the disease, resulting in significant prolongation of survival or cure.