Obesity is an established risk factor for several cancers, including breast, colon, endometrial, ovarian, gastric, pancreatic and liver, and is increasingly a public health concern. Obese cancer patients often have poorer prognoses, reduced response to standard treatments, and are more likely to develop metastatic disease than normo-weight individuals. Many of the pathologic features of obesity promote tumor growth, such as metabolic perturbations, hormonal and growth factor imbalances, and chronic inflammation. Although obesity exacerbates tumor development, the interconnected relationship between the two conditions presents opportunities for new treatment approaches, some of which may be more successful in obese cohorts. Here, we discuss the many ways in which excess adiposity can impact cancer development and progression and address potential preventive and therapeutic strategies to reduce the burden of obesity-related cancers.