Context: To systematically review and provide an informative synthesis of findings from longitudinal studies published since 1996 reporting on relationships between self-reported sedentary behavior and device-based measures of sedentary time with health-related outcomes in adults. Evidence acquisition: Studies published between 1996 and January 2011 were identified by examining existing literature reviews and by systematic searches in Web of Science, MEDLINE, PubMed, and PsycINFO. English-written articles were selected according to study design, targeted behavior, and health outcome. Evidence synthesis: Forty-eight articles met the inclusion criteria; of these, 46 incorporated self-reported measures including total sitting time; TV viewing time only; TV viewing time and other screen-time behaviors; and TV viewing time plus other sedentary behaviors. Findings indicate a consistent relationship of self-reported sedentary behavior with mortality and with weight gain from childhood to the adult years. However, findings were mixed for associations with disease incidence, weight gain during adulthood, and cardiometabolic risk. Of the three studies that used device-based measures of sedentary time, one showed that markers of obesity predicted sedentary time, whereas inconclusive findings have been observed for markers of insulin resistance. Conclusions: There is a growing body of evidence that sedentary behavior may be a distinct risk factor, independent of physical activity, for multiple adverse health outcomes in adults. Prospective studies using device-based measures are required to provide a clearer understanding of the impact of sedentary time on health outcomes.