© 2011 by Oxford University Press, Inc. All rights reserved. This chapter investigates the reasons why weight-loss maintenance is difficult and explores what is known about factors that contribute to successful weight-loss maintenance. The challenge is even greater with weight-loss maintenance while the goal during weight loss is to produce some degree of negative energy balance. The energy gap for weight-loss maintenance provides an estimate of the degree of behavior change required to maintain a given weight loss. The hope for successful long-term weight-loss maintenance comes with the second aspect of body-weight regulation that is unique to humans. Exercise may play a role in appetite regulation during weight-loss maintenance. Physical activity may be a key component of weight-loss maintenance not only because it serves to increase energy expenditure, but also because of a potential beneficial impact on appetite and energybalance regulation.