With energy intake restriction and exercise remaining the key diet and lifestyle approaches to weight loss, this is not without potential negative implications for body composition, metabolic health, and quality and quantity of life. Ideally, weight loss should be derived almost exclusively from the fat mass compartment as this is the main driver of metabolic disease, however, several studies have shown that there is an accompanying loss of tissue from the fat-free compartment, especially skeletal muscle. Population groups including post-menopausal women, the elderly, those with metabolic disease and athletes may be particularly at risk of skeletal muscle loss when following a weight management programme. Research studies that have addressed this issue across a range of population groups are reviewed with a focus upon the contribution of resistance and endurance forms of exercise and a higher intake dietary protein above the current guideline of 0.8 g/kg body weight/day. While findings can be contradictory, overall, the consensus appears that fat-free and skeletal muscle masses can be preserved, albeit to varying degrees by including both forms of exercise (but especially resistance forms) in the weight management intervention. Equally, higher intakes of protein can protect loss of these body compartments, acting either separately or synergistically with exercise. Elderly individuals in particular may benefit most from this approach. Thus, the evidence supports the recommendations for intakes of protein above the current guidelines of 0.8 g/kg body weight/d for the healthy elderly population to also be incorporated into the dietary prescription for weight management in this age group.