There is an epidemic of obesity, insulin resistance and cardiovascular disease. Adipose tissue plays a major metabolic role and produces hormones with important physiological effects. In vitro studies remove regulatory factors, such as blood flow, making results difficult to interpret, and animal studies cannot necessarily be extrapolated to humans. Fortunately, adipose tissue can be studied in vivo with microdialysis, adipose tissue vein cannulation, measurement of blood flow using 133Xenon washout, stable isotope tracers and biopsies. In vivo studies have shown that adipose tissue is an efficient buffer against the postprandial flux of non-esterified fatty acids (NEFA) in the circulation, protecting other tissues. When there is excess adipose tissue, this buffering effect may be impaired. The postprandial blood flow response is also reduced, potentially causing an atherogenic lipid profile and atheroma. A systems biology approach, combining in vivo techniques with genomics, proteomics and metabolomics, will clarify links between adipose tissue and vascular disease.