The primary purpose of this article was to examine the associations between life satisfaction level and health-related quality of life (HRQOL), chronic illness, and adverse health behaviors among adults in the U.S. and its territories. Data were obtained from the 2005 Behavioral Risk Factor Surveillance System, an ongoing, state-based, random-digit telephone survey of the noninstitutionalized U.S. population aged >or=18 years. An estimated 5.6% of U.S. adults (about 12 million) reported that they were dissatisfied/very dissatisfied with their lives. As the level of life satisfaction decreased, the prevalence of fair/poor general health, disability, and infrequent social support increased as did the mean number of days in the past 30 days of physical distress, mental distress, activity limitation, depressive symptoms, anxiety symptoms, sleep insufficiency, and pain. The prevalence of smoking, obesity, physical inactivity, and heavy drinking also increased with decreasing level of life satisfaction. Moreover, adults with chronic illnesses were significantly more likely than those without to report life dissatisfaction. Notably, all of these associations remained significant after adjusting for sociodemographic characteristics. Our findings showed that HRQOL and health risk behaviors varied with level of life satisfaction. As life satisfaction appears to encompass many individual life domains, it may be an important concept for public health research.