Recent decades have seen an unprecedented rise in obesity and the health impact thereof is increasingly evident. In 2014, worldwide more than 1.9 billion adults were overweight (BMI 25–29.9kg/m2) and of these over 600 million were obese (BMI≥30kg/m2). While the association between obesity and risk of diabetes and coronary artery disease is widely known, the impact of obesity on cancer incidence, morbidity and mortality is not fully appreciated. Obesity is associated with a higher risk of developing breast cancer, particularly in postmenopausal women, and is associated with worse disease outcome for women of all ages. The first part of this review summarizes the relationships between obesity and breast cancer development and outcome in pre and postmenopausal women and in hormone receptor positive and negative disease. The second part of this review addresses hypothesized molecular mechanistic insights that may underlie the effects of obesity to increase local and circulating pro-inflammatory cytokines that promote tumor angiogenesis, and stimulate the most malignant cancer stem cell population to drive cancer growth, invasion and metastasis. Finally, we review observational studies showing that increased physical activity associates with lower breast cancer risk and better outcome. We discuss effects of recent lifestyle interventions to decrease sex steroids, insulin/IGF-1 pathway activation and inflammatory biomarkers associated with worse breast cancer outcome in obesity. Although many observational studies show that exercise with weight loss associates with improved breast cancer outcome, further prospective studies are needed to determine if weight reduction will lead to improved patient outcome. It is hoped that several ongoing lifestyle intervention trials, reviewed herein, will support the systematic incorporation of weight loss intervention strategies into breast cancer patient care.