Decades of research have reported only weak associations between the intakes of specific foods or drinks and weight gain and obesity. Randomized controlled dietary intervention trials have only shown very modest effects of changes in nutrient intake and diet composition on body weight in obese subjects. This review summarizes the scientific evidence on the role mental stress (either in or not in association with impaired sleep) may play in poor sleep, enhanced appetite, cravings and decreased motivation for physical activity. All these factors contribute to weight gain and obesity, possibly via decreasing the efficacy of weight loss interventions. We also review evidence for the role that lifestyle and stress management may play in achieving weight loss in stress-vulnerable individuals with overweight.