Purpose Obesity (body mass index [BMI] ≥ 30 kg/m2) is common among patients with cancer. We reviewed management issues in the obese patient with cancer, focusing on how obesity influences treatment selection (including chemotherapy dosing), affects chemotherapy toxicity and surgical complications, and might be a treatment effect modifier. Methods The majority of evidence is drawn from observational studies and secondary analyses of trial data, typically analyzed in N × 3 BMI categories (normal weight, overweight, and obese) matrix structures. We propose a methodological framework for interpretation focusing on sample size and composition, nonlinearity, and unmeasured confounding. Results There is a common perception that obesity is associated with increased treatment-related toxicity. Accordingly, cytotoxic chemotherapy dose reduction is common in patients with elevated BMI. Contrary to this, there is some evidence that full dosing in obese patients does not result in increased toxicity. However, these data are from a limited number of regimens, and fail to fully capture cytotoxic drug pharmacodynamics and pharmacokinetic variability in obese patients. Among patients undergoing surgery, there is evidence that elevated BMI is associated with increased perioperative mortality and increased rates of infectious complications. A novel finding is that these relationships hold after surgery for malignancy, but not for benign indications. There are biologic plausibilities that obesity might be an effect modifier of treatment, but supporting evidence from clinical studies is inconsistent. Conclusion In line with the ASCO 2012 guidelines, chemotherapy dosing is probably best performed using actual body weight in obese patients. However, specific regimens known to be associated with increased toxicity in this group should be used with caution. There is no guidance on dose for obese patients treated with biologic agents. Currently, there are no specific recommendations for the surgical management of the obese patient with cancer.