The incidence of obesity is increasing rapidly. Research efforts for effective treatment strategies still focus on diet and exercise programmes, the individual components of which have been investigated in intervention trials in order to determine the most effective recommendations for sustained changes in bodyweight. The foremost objective of a weight-loss trial has to be the reduction in body fat leading to a decrease in risk factors for metabolic syndrome. However, a concomitant decline in lean tissue can frequently be observed. Given that fat-free mass (FFM) represents a key determinant of the magnitude of resting metabolic rate (RMR), it follows that a decrease in lean tissue could hinder the progress of weight loss. Therefore, with respect to long-term effectiveness of weight-loss programmes, the loss of fat mass while maintaining FFM and RMR seems desirable. Diet intervention studies suggest spontaneous losses in bodyweight following low-fat diets, and current data on a reduction of the carbohydrate-to-protein ratio of the diet show promising outcomes. Exercise training is associated with an increase in energy expenditure, thus promoting changes in body composition and bodyweight while keeping dietary intake constant. The advantages of strength training may have greater implications than initially proposed with respect to decreasing percentage body fat and sustaining FFM. Research to date suggests that the addition of exercise programmes to dietary restriction can promote more favourable changes in body composition than diet or physical activity on its own. Moreover, recent research indicates that the macronutrient content of the energy-restricted diet may influence body compositional alterations following exercise regimens. Protein emerges as an important factor for the maintenance of or increase in FFM induced by exercise training. Changes in RMR can only partly be accounted for by alterations in respiring tissues, and other yet-undefined mechanisms have to be explored. These outcomes provide the scientific rationale to justify further randomised intervention trials on the synergies between diet and exercise approaches to yield favourable modifications in body composition.