Purpose of reviewTo highlight the underexposed but important role of protein in food intake and body weight regulation.Recent findingsProtein plays a key role in food intake regulation through satiety related to diet-induced thermogenesis. Protein also plays a key role in body weight regulation through its effect on thermogenesis and body composition. A high percentage of energy from dietary protein limits body weight (re)gain through its satiety and energy inefficiency related to the change in body composition.SummaryProtein is more satiating than carbohydrate and fat in the short term, over 24 h and in the long term. Thermogenesis plays a role in this satiety effect, but the role of satiety hormones still needs to be elucidated. On the short-term ‘fast’ proteins are more satiating than ‘slow’ proteins, and animal protein induces a higher thermogenesis than vegetable protein. In the longer term the higher postabsorptive satiety and thermogenesis are sustained irrespective of the protein source. High-protein diets affect body weight loss positively only under ad-libitum energy intake conditions, implying also a decreased energy intake. Body composition and metabolic profile are improved. Additional protein consumption results in a significantly lower body weight regain after weight loss, due to body composition, satiety, thermogenesis, and energy inefficiency, while the metabolic profile improves. Implications from these findings are: for practice, recommendations for increasing the percentage of energy from protein while reducing energy intake; for clinical research, assessment of the paradox of increasing the percentage energy from a highly satiating macronutrient; of the potential roles of protein in a negative and positive energy balance; assessment of possibilities of replacing dietary protein by effective amino acids or peptides that may show a similar impact on body weight regulation.