This systematic review assesses the long‐term effectiveness of weight loss on all cause mortality in overweight/obese people. Medline, Embase and Cinahl were searched (1966–2005). Cohort studies and trials on participants with body mass index ≥25 kg m⁻², with weight change and mortality with ≥2‐year follow‐up, were included finally identifying 11 papers based on eight studies. There may be gender differences in the benefits for all cause mortality. The impact of weight loss in men on mortality was not clear with some studies indicating weight loss to be detrimental, while a recent cohort study showed benefits, if it were a personal decision. Other studies with no gender separation had similarly mixed results. However, one study indicated that overweight/obese women with obesity‐related illness, who lost weight intentionally within 1 year, had significantly reduced mortality rates of 19–25%. In contrast, studies of overweight/obese diabetics irrespective of gender showed significant benefit of intentional weight loss on mortality in a meta‐analysis, hazard ratios = 0.75 (0.67–0.83). There is some evidence that intentional weight loss has long‐term benefits on all cause mortality for women and more so for diabetics. Long‐term effects especially for men are not clear and need further investigation.