The objective of this study was to overview high-qualitative systematic reviews to synthesize the evidence for associations between sedentary behavior and health outcomes in adults. There is evidence for a cross-sectional association between accelerometer measured sedentary time and poorer insulin sensitivity, and an association between sedentary breaks and BMI/waist circumference and triglycerides. Based on intervention studies (only randomized cross-over), there is evidence for an association between prolonged sitting and some markers for poorer cardiovascular health, but it is unclear whether this may be generalized to adults in general. There is also evidence to support an association between self-reported sedentary behavior (e.g., screen-time and total sitting time) and cardiovascular disease incidence and death, cancer incidence and death, and all-cause mortality. The inconsistent use of sedentary measures suggests, however, that caution is required when interpreting the results.