Obesity has reached epidemic proportions and is one of the greatest challenges for public health in the twenty-first century. The macronutrient composition of diets, in particular the amount and ratio of carbohydrates, fat and protein, have received considerable attention in recent decades due to its potential relevance to the development of obesity and weight loss. The effects of various macronutrients on body weight regulation are still under debate. High-carbohydrate diets, and particularly high-fat diets, have been blamed for the increase in the prevalence of obesity. This paper shows that neither fat nor carbohydrates are fattening per se. Mixed diets with substantial amounts of fat and high-glycemic carbohydrates, like current WDs, are required to promote weight gain and obesity. High-glycemic carbohydrates are the active partner (the "driver"), which promotes fat storage through its insulinogenic effect, while fat is the passive partner (the "passenger") on the way to obesity. Elevated insulin levels (postprandial, but more importantly due to hypersecretion and hyperinsulinemia) promote fat storage and play a key role in obesogenesis and the obesity epidemic. Furthermore, mixed diets high in high-glycemic carbohydrates and fat promote fetal programming, with long-term adverse impacts on the offspring, including insulin hypersecretion, (childhood) obesity and metabolic diseases. Maternal obesity and high weight gain during pregnancy have also been linked to deleterious effects on fetal programming. As the global obesity epidemic increasingly affects women of reproductive age, a significant percentage of fetuses will experience fetal programming with a tendency towards obesity - a self-reinforcing process that further fuels the epidemic. A change in lifestyle and diet composition is needed to prevent or limit the development of obesity and related diseases.