The problem of overweight and obesity has reached epidemic proportions in the United States and globally, and the high prevalence is due in part to the recidivism associated with weight loss treatment. Approximately one-third of lost weight is often regained in the first year after treatment and, at times, continues. Because a plethora of comorbid diseases are associated with obesity, in particular, cardiovascular disease, hypertension, and hyperlipidemia, clinicians and researchers have attempted to find useful strategies for maintaining weight loss. This review presents the findings from 42 randomized clinical trials of weight loss maintenance from 1984 through 2007 using interventions that include (1) the Internet, (2) strategies after a very low calorie diet, (3) pharmacotherapy, (4) behavioral strategies, (5) physical activity, and (6) alternative strategies. The results of the reviewed trials revealed that treatment with orlistat or sibutramine combined with dietary modification, caffeine or protein supplementation, consuming a diet lower in fat, adherence to physical activity routines, prolonged contact with participants, problem-solving therapy, and the alternative treatment of acupressure were efficacious in reducing weight regain after weight loss treatment. The limitations of some studies may reduce the robustness of their findings, and future studies are necessary to replicate and support these results so that individuals are able to maintain weight loss and retain the health benefits associated with a lower weight.