Lifestyle factors, particularly obesity, have been associated with poor breast cancer outcomes in a large number of observational studies. Despite a growing body of research, controversy exists regarding obesity associations across breast cancer subtypes and the importance of obesity versus physical activity and dietary composition in determining breast cancer outcome. These controversies are reviewed and the complex biologic nature of the association of obesity with breast cancer addressed. Potential mediators, including insulin, estrogens, adipokines and inflammation markers are identified. Relevant prognostic findings of previous research involving dietary, physical activity and weight loss interventions are summarized. A broad-based program of research is outlined, highlighting the need for a randomized trial of weight loss that is adequately powered to examine survival effects, as well as correlative and preclinical research to investigate mediators and mechanisms of obesity effects on breast cancer outcomes. Finally, potential contributions of alcohol intake and tobacco use in breast cancer survivors are discussed.