Body-weight management requires a multifactorial approach. Recent findings suggest that an elevated protein intake seems to play a key role herein, through (i) increased satiety related to increased diet-induced thermogenesis; (ii) its effect on thermogenesis; (iii) body composition; and (iv) decreased energy-efficiency, all of which are related to protein metabolism. Supported by these mechanisms, relatively larger weight loss and subsequent stronger body-weight maintenance have been observed. Increased insulin sensitivity may appear, but it is unclear whether this is due to weight loss or type of diet. The phenomenon of increased satiety is utilized in reduced energy-intake diets, mainly in the ad libitum condition, whereby sustained satiety is achieved with sustained absolute protein intake in grams, despite lower energy intake. Elevated thermogenesis and glucagon-like peptide-1 (GLP-1) appear to play a role in high-protein induced satiety. Under conditions of weight maintenance, a high-protein diet shows a reduced energy efficiency related to the body composition of the body weight regained, that is, in favor of fat-free mass. Indeed, during body-weight loss, as well as during weight regain, a high-protein diet preserves or increases fat-free mass and reduces fat mass and improves the metabolic profile. In the short-term this may be supported by a positive protein and a negative fat balance, through increased fat oxidation. As protein intake is studied under various states of energy balance, absolute and relative protein intake needs to be discriminated. In absolute grams, a normal protein diet becomes a relatively high-protein diet in negative energy balance and at weight maintenance. Therefore, 'high protein negative energy balance diets' aim to keep the grams of proteins ingested at the same level as consumed at energy balance, despite lower energy intakes.International Journal of Obesity (2006) 30, S16-S23. doi:10.1038/sj.ijo.0803487. AD -  1Department of Human Biology, Nutrim, Maastricht University, MD Maastricht, The Netherlands  2Wageningen Centre of Food Sciences, Wageningen, The Netherlands.