Obesity is a chronic disorder caused by an imbalance of the energy metabolism. The costs associated with excessive weight gain are very high and big efforts are carried out in studying new types of hipocaloric diets and their composition, so that the therapy of obesity is more specific, long lasting and safe. At the moment, various investigations are trying to determine the specific influence of the macronutrient distribution on the regulation of body weight. Very low calorie diets (VLCD) supplying between 400 and 800 Kcal/day have been beneficial in short-term treatments causing a weight loss of 300-500 g/day. However, these strategies emphasise more on calorie restriction than on macronutrient composition. Weight loss produced by either low carbohydrate fat or low fat moderately energy restricted diets ranges from 0.5-1.0 kg/week. These diets when consumed ad libitum, but guided to low fat consumption, or a high fat low carbohydrate intake produce a weight loss of 0.2-0.4 kg/week. However, there are other factors that determine weight loss induced by dieting such as gender, age, initial body weight, race, genetics, regional fat deposition, etc. More research is needed, particularly on studies about the impact of those diets with different fuel substrates on the characteristics of the weight loss and changes in blood lipid profile.