BACKGROUND: Mounting evidence, particularly from prospective epidemiologic studies but with additional support from animal models and mechanistic studies, supported conclusions in 2016 by the International Agency for Research on Cancer (IARC) in their review of the preventive effects of weight control on cancer risk. CONTENT: The workgroup concluded that obesity is causally related to cancer at 13 anatomic sites (esophagus: adenocarcinoma; gastric cardia; colon and rectum; liver; gallbladder; pancreas; breast: postmenopausal; uterine endometrial; ovary; kidney: renal cell; meningioma; thyroid; and multiple myeloma). Further, avoiding weight gain and excess body fat will prevent cancer. Evidence on weight loss and reduction in risk of cancer is more limited. Ongoing clinical trials address the benefits of weight loss interventions after diagnosis. SUMMARY: Here, we review the evidence from the 2016 IARC that obesity is causally related to cancer at 13 anatomic sites and identify areas for future research, including the consequences of childhood adiposity, the relation between velocity of weight gain and cancer risk, and improved methods for analysis of life-course adiposity and cancer risk. Refining understanding of mechanisms may further inform prevention strategies.