While the stress associated with acute exercise has been reported to induce significant lymphocyte apoptosis, not all investigations have confirmed this finding. Regardless of animal or human subjects, exercise-induced lymphocyte apoptosis may be induced via an external receptor-mediated pathway, or internally via the mitochondria through an oxidative-mediated pathway. On the other hand, investigators reporting no effect of acute exercise on lymphocyte apoptosis speculate that cell death may be dissociated from these pathways, and explain exercise lymphocytopenia by selective migration of the lymphocytes back into the lymphoid pools. Discrepancies may be due to sensitivity issues related to the methodology used to assess cell death. Limitations to various methods used to evaluate exercise-induced lymphocyte apoptosis are detailed, and considerations for a new technique are outlined.