Anti-angiogenic therapy, predominantly with the anti-VEGF antibody bevacizumab, has not been shown to improve the survival of patients with breast cancer. 70% of patients with this disease are overweight or obese; now, data from 99 patients treated with bevacizumab indicate that a high BMI (≥25) is associated with tumours that are typically larger at diagnosis, hypovascular, hypoxic, and insensitive to bevacizumab. Interestingly, patients with a high BMI had high circulating levels of IL-6 and FGF2. In obese mice with breast cancer, elevated expression of FGF2 or IL-6 by adipocytes and other cells of the tumour microenvironment was likewise associated with resistance to anti-VEGF therapy, which could be overcome through pharmacological antagonism of the FGF2 or IL-6 axes.