In a recent study conducted in a cohort of 52 septic patients, Monserrat and coworkers found that profound failure of peripheral T cells to convert from a naïve phenotype to an activated phenotype has positive predictive value in identifying patients who do not recover. These data support the hypothesis that failure of the innate immune system to engage the T-cell compartment contributes to sepsis mortality and provides motivation for the development and clinical evaluation of immunostimulatory therapies for patients with sepsis.