The health benefits of caloric restriction (CR) are numerous and have been demonstrated in various animal models. These benefits include increased longevity and delayed onset of age-related disorders such as cardiovascular diseases, diabetes, neurological disorders and cancer. Health benefits of CR in humans are harder to demonstrate, but indirect evidences point toward similar improvements. However, prolonged CR is difficult to sustain in humans, and a period of CR is often followed by a period of excess caloric intake which drives weight regain and is often associated with unhealthy effects. After growth arrest by CR in rats, refeeding (even on the same amount of food calories as control animals) results in preferential fat accumulation and hyperinsulinemia. Furthermore, rats submitted to repeated cycles of CR followed by caloric excess (a model of yoyo dieting), in comparison to control rats on a fixed isocaloric food intake, exhibit fat accumulation and insulin resistance independently of excess weight gain. In humans, there is now compelling evidence for increased cardiovascular risks in response to weight cycling, possibly linked to hypertension, visceral fat accumulation, insulin resistance and dyslipidemia. Moreover, fluctuations in blood pressure, heart rate, sympathetic activity, glomerular filtration rate, blood glucose and lipids during weight cycling - with overshoots above normal values during weight regain periods - put an additional load on the cardiovascular system.