Hodgkin's lymphoma (HL) has a unique and distinct history, epidemiology, treatment, and biology. A viral agent or infectious agent has long been considered as the etiologic agent and Epstein-Barr virus is the main candidate for the infectious agent causing HL; however, Epstein-Barr virus genome is found within the tumor in only about 20% to 40% of HL cases with a prior diagnosis of infectious mononucleosis. Recently, autoimmune and related conditions have drawn attention to a potential role for immune-related and inflammatory conditions in the etiology and pathogenesis of the malignancy. Evidence from multiply-affected families, a twin study, a case-control study, and population-based registry studies implicate genetic factors. Data from Eastern Asia and among Chinese immigrants in North America indicate increasing incidence trends for HL being associated with westernization. These results emphasize an interaction between environmental and genetic risk factors in HL.