Psychosocial issues are an understudied yet important concern in the overall health of hemodialysis (HD) patients. Stress is a concomitant of chronic illness and its treatment, and may have meaningful influences on psychological and medical outcomes. This article reviews the influences of psychopathology, social support, family issues, dialysis unit culture, and socioeconomic status on patients treated with center HD. Depressive affect and decreased perception of social support have been linked with mortality in several studies of ESRD patients. Decreased marital satisfaction, disturbances in family dynamics, and lower socioeconomic status (SES) have been associated with poorer health outcomes and can affect patients' perception of social support and depressive affect. Chronically ill ESRD patients who undergo treatment with constant interaction and observation by medical staff are potentially an ideal group for evaluation of the effects of stress and psychosocial factors on outcomes in those with chronic disease, as well as an excellent patient population for intervention to reduce morbidity and mortality. These interactions between potentially modifiable psychosocial risk factors for disease and medical aspects of illness form a paradigm for the study of interventions related to adjustment to chronic illness in the ESRD population.