Genital herpes virus infection is one of the most prevalent and perhaps the most emotionally difficult of the sexually transmitted diseases. This article examines the current empirical and clinical understanding of the psychosocial aspects of the disease and proposes a framework for future investigation. Psychosocial issues of importance in the disease are discussed and responses characteristic of the psychosocial adjustment process are presented. Evidence of the role of stress and psychosocial factors is reviewed. Finally, a biopsychosocial research approach to the psychoneuroimmunological mechanisms of the disease is suggested as a way of understanding etiology and process.