Obesity in middle-aged humans is a risk factor for many age-related diseases and decreases life expectancy by about 7 years, which is roughly comparable to the combined effect of all cardiovascular disease and cancer on life span. The prevalence of obesity increases up until late middle age and decreases thereafter. Mechanisms that lead to increased obesity with age are not yet well understood, but current evidence implicates impairments in hypothalamic function, especially impairments in the ability of hypothalamic pro-opiomelanocortin neurons to sense nutritional signals. The rapid increase in the prevalence of obesity at all ages in the past decade suggests that, in the next two or three decades, diseases associated with obesity, especially diabetes, will begin to rise rapidly. Indeed, these trends suggest that for the first time in modern history, the life expectancy of people in developed societies will begin to decrease, unless the rapid increase in the prevalence of obesity can be reversed.