This chapter presents the epidemiologic evidence on the association between physical activity and hematologic cancers and related hypothesized biologic mechanisms. Some preliminary indications of a protective role for physical activity for non-Hodgkin's lymphoma, leukemia, multiple myeloma, and Hodgkin's lymphoma exist, but the level of epidemiologic evidence is still insufficient to make any definitive conclusions regarding the nature of these associations. Several plausible biologic mechanisms underlying the possible associations between physical activity and hematologic cancers have been proposed, including enhancement of immune function, reduction in obesity, improvement of antioxidant defense systems, impact on metabolic hormones, and anti-inflammatory effects. Future studies should improve the estimation of physical activity by using more reliable, valid, and comprehensive measurement tools, assessing all components of physical activity (type, intensity, and time period), and conducting intervention studies to evaluate the effect of physical activity on various biomarkers of cancer in order to provide further insight into plausible biologic mechanisms underlying the possible association between physical activity and hematologic cancers.