The main objective of this study was to examine the mediational and moderational effect of exercise, diet, and stress management on the relationship between functional disability and health-related quality of life. Quantitative descriptive research design using multiple regression and correlation techniques was used. Participants were 215 individuals with multiple sclerosis (MS). Outcome measure used was health-related quality of life as measured by the Medical Outcomes Study (MOS) Short-Form Health Survey (SF-12v2). Functional disability and health-promoting behaviors including exercise, diet, and stress management were found to be associated with health-related quality of life. Exercise and stress management (but not diet) were partial mediators between functional disability and health-related quality of life. Exercise was found to be a moderator between functional disability and health-related quality of life. Exercise had a stronger effect on health-related quality of life for individuals with lower functional disability than people with higher functional disability. Health-promoting behaviors are important for health-related quality of life, and health-related quality of life in turn is related to better employment outcomes. Health-promoting behaviors can also mediate the relationship between functional disability and health-related quality of life. Rehabilitation counselors should consider including health promotion interventions in vocational rehabilitation services for individuals with MS. (Contains 1 table and 2 figures.)