The specific metabolic contribution of consuming different energy-yielding macronutrients (namely, carbohydrates, protein and lipids) to obesity is a current topic of debate. A recent review summarizes the existing evidence concerning associations between the intake of different macronutrients with weight gain and adiposity. Overall, current evidence suggests that energy surplus is the main driver of overweight and obesity. On the contrary, the question of refined sugars and some fats playing complementary roles in weight gain and whether calories from different macronutrients count as equal still remain very controversial. In this regard, dietary patterns particularly rich in sources of monounsaturated fats, such as extra virgin olive oil in the Mediterranean diet, have been inversely associated with BMI. This highlights the importance of the fat profile and not just the total amount of fat or differences attributed to genetic background.