The purpose of this report is to review the evidence that physical inactivity and excess adiposity are related to an increased risk of all-cause mortality, and to better identify the independent contributions of each to all-cause mortality rates. A variance-based method of meta-analysis was used to summarize the relationships from available studies. The summary relative risk of all-cause mortality for physical activity from the 55 analyses (31 studies) that included an index of adiposity as a covariate was 0.80 [95% confidence interval (CI) 0.78–0.82], whereas it was 0.82 [95% CI 0.80–0.84] for the 44 analyses (26 studies) that did not include an index of adiposity. Thus, physically active individuals have a lower risk of mortality by comparison to physically inactive peers, independent of level of adiposity. The summary relative risk of all-cause mortality for an elevated body mass index (BMI) from the 25 analyses (13 studies) that included physical activity as a covariate was 1.23 [95% CI 1.18–1.29], and it was 1.24 [95% CI 1.21–1.28] for the 81 analyses (36 studies) that did not include physical activity as a covariate. Studies that used a measure of adiposity other than the BMI show similar relationships with mortality, and stratified analyses indicate that both physical inactivity and adiposity are important determinants of mortality risk.