Epidemiologic evidence points to obesity as a major risk factor for many cancers, including cancers of the breast, endometrium, colorectum, kidney, oesophagus and pancreas. Whether intentional weight loss might reduce this excess risk is not yet proven. We searched the medical literature for studies reporting changes in cancer risk following intentional weight loss, and for studies reporting changes in cancer-relevant risk factors of oestrogens, sex hormone binding globulin (SHBG), Insulin-like growth factor-I (IGF-I), IGF binding proteins and selected inflammatory markers [C-reactive protein (CRP), interleukin 6 (IL-6) and tumour necrosis factor-α (TNF-α)]. Observational cohort studies and randomized controlled trials of both dietary interventions and bariatric surgery all indicate fairly immediate reductions in cancer incidence following intentional weight loss. Oestrogen levels drop and SHBG levels increase coincident with intentional weight loss, with about a one-third reduction in free oestradiol to be expected from a 10% weight loss. CRP levels also drop substantially after weight loss at about this same 3 : 1 ratio. Reductions in TNF-α and IL-6 are consistently seen, but of a smaller magnitude, and IGF-I and IGFBP changes after weight loss are small and inconsistent. Because both cancer incidence and levels of circulating cancer biomarkers drop fairly rapidly following weight loss, intentional weight loss may well lead to meaningful reductions in cancer risk with a short latency time.