Obesity and knee osteoarthritis (OA), two of the most common chronic diseases, are often comorbid. Obesity increases the risk of knee OA by a variety of mechanisms, such as increased joint loading and changes in body composition, with detrimental effects related to metainflammation and behavioural factors, including diminished physical activity and subsequent loss of protective muscle strength. These complex interactions present a challenge to the managing physician. The risk of knee OA related to weight gain and obesity begins from an early age. Weight loss reduces the risk of incident knee OA, and, in established disease, reduces symptoms, improves function and is likely to reduce disease progression. We review strategies to facilitate weight loss, with particular reference to their application in people with knee OA. Although knee OA presents intrinsic barriers to weight management, weight loss is possible at all stages of disease. Exercise or muscle strengthening are desirable for general health and to improve function, but are not essential to achieve weight loss and a successful symptomatic result. The degree of weight loss required to achieve benefit might be greater with increasing disease severity. Finally, we outline the need for a societal approach to tackle obesity-related OA.