There is substantial evidence of individual variation in health-related quality of life measures that is not accounted for by age or disease condition. An understanding of factors that determine good health is necessary for maintained function and improved quality of life. This study examines the extent to which social support and stressful life events were more or less beneficial for the long-term physical functioning and emotional well-being of 1402 chronically ill patients. Analyses, conducted separately in three age groups, showed that social support was beneficial for health over time regardless of age. In addition, low levels of support were particularly damaging for the physical functioning of older patients. Stressful life events impacted differentially on health-related quality of life: relationship events had an immediate effect on well-being which diminished with time; financial events had an immediate negative effect on functioning and well-being which persisted over time for middle-aged patients; bereavement had a delayed impact on quality of life, with the youngest patients especially vulnerable to its negative effects; work-related events had both negative and positive effects, depending on age group. Results reinforce the importance of identifying and dealing with psychosocial problems among patients with chronic diseases.