What does a clinician need to know about low-carbohydrate (LC) diets? This review examines and compares the safety and the effectiveness of a LC approach as an alternative to a low-fat (LF), high-carbohydrate diet, the current standard for weight loss and/or chronic disease prevention. In short-term and long-term comparison studies, ad libitum and isocaloric therapeutic diets with varying degrees of carbohydrate restriction perform as well as or better than comparable LF diets with regard to weight loss, lipid levels, glucose and insulin response, blood pressure, and other important cardiovascular risk markers in both normal subjects and those with metabolic and other health-related disorders. The metabolic, hormonal, and appetite signaling effects of carbohydrate reduction suggest an underlying scientific basis for considering it as an alternative approach to LF, high-carbohydrate recommendations in addressing overweight/obesity and chronic disease in America. It is time to embrace LC diets as a viable option to aid in reversing diabetes mellitus, risk factors for heart disease, and the epidemic of obesity.