Psychoneuroimmunology (PNI) is the study of the interrelationships among behavior, neural and endocrine function, and the immune system. PNI investigates the relationships among stress, physiological dysregulation, and health outcomes. Research has supported the theory that emotional distress and the resultant neuroendocrine activation can induce immune system suppression. This suppression has significant implications for disease susceptibility and progression. HIV disease and its extensive immunological consequences are explored within this framework. Potential physiological pathways that may mediate stress-induced dysregulation within the context of HIV disease are identified. Key HIV-related PNI research studies are reviewed and critically analyzed. Implications for nursing practice and research are discussed.