At least one-third of Americans are obese, as defined by body mass indexes corresponding to body weight > or = 120% of ideal body weight, and this figure is rising steadily. Women and nonwhites have particularly high rates of obesity. Obesity greatly increases risks for many serious and morbid conditions, including diabetes mellitus, hypertension, dyslipidemia, coronary artery disease, and some cancers. Obesity is clearly associated with increased risk for mortality, but there has been controversy regarding optimal weight with respect to mortality risk. We review the literature concerning obesity and mortality, with reference to body fat distribution and weight gain, and consider potential effects of sex, age, and race on this relation. We conclude that when appropriate adjustments are made for effects of smoking and underlying disease, optimal weights are below average in both men and women; this appears to be true throughout the adult life span. Central obesity, most commonly approximated by the waist-to-hip ratio, may be particularly detrimental, although this requires further study. Weight gain in adulthood is also associated with increased mortality. These observations support public health measures to reduce obesity and weight gain, including recent recommendations to limit weight gain in the adult years to 4.5 kg (10 lb).