The sepsis syndrome is characterized by the acute release of a variety of inflammatory mediators, which often result in detrimental effects to the host. The release of these mediators is regulated and counterbalanced by the coordinated expression of antiinflammatory molecules. It is the balance between the expression of pro- and antiinflammatory mediators that often determines the magnitude of early tissue injury and subsequent risk of infectious complications. As our understanding of the pathophysiology of sepsis continues to evolve, we have gained a greater appreciation for the effects that sepsis and similar states of overwhelming stress have on host antimicrobial immunity. A number of functional defects in leukocytes isolated from sepsis patients have been characterized. These defects include diminished expression of important cell surface antigens, dysregulated cytokine production, alterations in antigen-presenting ability, and accelerated apoptosis. Impaired leukocyte function has important clinical ramifications, as high mortality rates have been observed in patients displaying evidence of sepsis-induced immune deactivation. In this article, we review the current literature supporting evidence of dysregulation of host immunity occurring during sepsis syndrome, characterize the underlying pathophysiology, and describe novel therapeutic interventions directed at augmenting host immunity during sepsis.