Non-Hodgkin lymphoma (NHL) consists of many histologically and biologically distinct lymphoid malignancies with poorly understood, but possibly distinct, etiologies. The patterns of incidence and time trend vary not only by age, sex, and race/ethnicity in the USA, but also show significant geographic differences, suggesting the potential role of infectious agents, environmental factors, and lifestyle factors in addition to host genetic status in the development of NHL. Important pathogenetic mechanisms include immune modulation and chronic antigen stimulation. Epidemiologic studies in the past two decades have provided intriguing new insights on the possible causes of lymphoma and support the idea that there is some mechanistic commonality of lymphomagenesis, but significant etiologic heterogeneity clearly exists. This review presents a summary of the current understanding of the descriptive epidemiology and etiology of NHL and suggests areas of focus for future epidemiologic research.