A large body of epidemiological evidence links obesity to increased cancer incidence, with some studies also indicating poorer survival in obese patients with cancer. Obese patients face several specific challenges related to diagnosis and treatment of cancer. Reduced participation in cancer screening programmes, lower tumour-marker expression and issues with medical imaging among obese individuals complicate cancer diagnosis. Chemotherapy and hormonal therapy in obese patients with cancer is affected by altered pharmacokinetics and hormone levels. In addition, the precision of radiotherapy might be adversely affected in this population by greater skin motility and increased motion of internal organs. Obese patients also face higher risk of minor complications after surgery. There is a need for additional research addressing issues specifically associated with the clinical management of obese patients with cancer, including comorbidity, polypharmacy, and problems related to sarcopenia and health-related quality of life. This Review summarizes the available literature addressing the clinical management of obese patients with cancer and discusses opportunities to improve the cancer care of these patients.