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The benefits of aerobic moderate‐to‐vigorous physical activity (MVPA) on major non‐communicable diseases (NCDs) are well established. However, much less is known whether muscle‐strengthening activities (i.e., resistance/weight/strength training) confer similar benefits. Herein, we conducted a narrative literature review and summarized the existing evidence from large prospective cohort studies on muscle strengthening activities and risk of major chronic diseases and mortality in adults generally free of major NCDs at baseline. Current epidemiologic evidence suggests that engagement in muscle‐strengthening activities over 1–2 sessions (or approximately 60–150 min) per week was associated with reduced risk of cardiovascular disease (seven studies; approximately 20%–25% reduction), type 2 diabetes (four studies; approximately 30% reduction), cancer mortality (four studies; approximately 15%–20% reduction) as well as all‐cause mortality (six studies; approximately 20%–25% reduction). For diabetes, the risk appears to lower further with even higher levels of muscle‐strengthening activities, but some studies for cardiovascular and all‐cause mortality suggest a reversal whereby higher levels (≥2.5 h/week) have less benefit, or are even harmful, relative to lower levels of activity. The likely mechanisms contributing to a benefit include improvement in body composition, lipid profile, insulin resistance and inflammation. The evidence supports engaging in 1–2 sessions (up to 2.5 h) per week, preferably performed complementary to the recommended levels of aerobic MVPA. Although data are limited, caution is suggested for training exceeding 2.5 h per week. Further studies are required to better understand the influence of frequency, duration and intensity of muscle‐strengthening activities on major NCDs and mortality in diverse populations. [ABSTRACT FROM AUTHOR]