Several expert panels have recommended that obese individuals attempt to lose 10% of their initial body weight through a combination of diet, physical activity, and behavior therapy (frequently referred to as lifestyle modification). This article reviews the short-and long-term results of lifestyle modification and methods to improve them. Randomized controlled trials were examined that compared different diet and activity interventions for inducing and maintaining weight loss. Studies that compared different methods of providing lifestyle modification, including on-site vs. Internet-based delivery, also were examined. A comprehensive lifestyle modification program was found to induce a loss of approximately 10% of initial weight in 16 to 26 weeks of group or individual treatment, delivered on-site. Comprehensive Internet-based programs induced a loss of approximately half this size. Patients' consumption of portion-controlled diets, including liquid meal replacements, was associated with significantly greater short-term weight loss than was the consumption of isocaloric diets comprised of conventional foods. Factors associated with long-term weight control included continued patient-practitioner contact (whether on-site or by e-mail), high levels of physical activity, and the long-term use of pharmacotherapy combined with lifestyle modification. In summary, lifestyle modification induces clinically significant weight loss that is associated with the prevention or amelioration of cardiovascular risk factors.