Recent research indicates that T-lymphocyte dysfunction may contribute to sepsis-associated morbidity and mortality. B and T lymphocyte attenuator (BTLA) is a co-inhibitory receptor expressed by T lymphocytes and B lymphocytes that is important in regulating lymphocyte activation during inflammation and infection. Shubin and colleagues report that higher mean BTLA expression in critically ill patients may have value in identifying patients with infection. Further studies provide evidence that BTLA activation contributes to T-lymphocyte apoptosis during sepsis. Although this study will require follow-up and further investigation, the results advance current knowledge regarding potential mechanisms underlying sepsis-induced immunosuppression and identify BTLA as a candidate biomarker and mediator of T-cell dysfunction during sepsis.