Sepsis is the commonest cause of admission to medical ICUs across the world. Mortality from sepsis continues to be high. Besides shock and multi-organ dysfunction occurring following the intense inflammatory reaction to sepsis, complications arising from sepsis-related immunoparalysis contribute to the morbidity and mortality from sepsis. This review explores the basis for sepsis related immune dysfunction and discusses its clinical implications for the treating intensivist. Recent trends indicate that a significant proportion of septic patients succumb to the complications of secondary infections and chronic critical care illness from the initial bout of sepsis. Therefore care-givers in the ICU need to be aware of the impediments posed by sepsis-related immune dysfunction that can impair recovery in patients with sepsis and contribute to sepsis-related mortality.