In general, treatment of obesity results in only relatively moderate weight loss (5-10%). Another major problem is long-term weight loss maintenance. The reason for the weight regain after weight loss is related to both psychological and basal physiological mechanisms. In this review we summarise the research from both animal and human studies showing that there are powerful physiological reactions that can be detected in association with weight loss. Weight loss seems to result in a pronounced stimulation of the appetite and a long-lasting fall in both the basal and exercise-induced metabolic rates. These energy-conserving mechanisms may partially explain the difficulty in maintaining weight loss.