Carbohydrates (CHO) and lipids provide the amount of energy required for physical and chemical reactions inside the human body. The various constraints the body has to resolve explain the use of these two substrates, catabolized via distinct pathways to one common final reaction. In the classic model, three main organs/tissues for substrate fluxes (liver, adipose tissue and skeletal muscle) and one organ regulating main reactions by adaptation of hormonal secretions (endocrine pancreas) are described. From this point of view, the only interactions between CHO and lipid metabolisms are mediated by glycaemic changes via insulin/glucagon ratio (IGR). However, according to recent advances, this concept seems to have a limited validity as it does take into account neither the many other interactions between CHO and lipid metabolism that are likely to occur in addition to the coarse control by IGR, nor the long-term regulation of energy balance, whose description began with the discovery of leptin. Moreover, it does not include the effects of energy expenditure. Therefore, this review focuses on three topics: (i) describe interactions between CHO and lipid metabolism at the level of each tissue and organ implied, via hormonal signaling as well as direct action of nutrients, (ii) integrate fluxes of substrates and signals between those tissues at rest in a global view of the metabolism taking into account short-term and long-term regulating factors and (iii) describe separately, to avoid confusion or extrapolation, the short-term and long-term influence of exercise on these regulation loops.