Obesity and obesity-associated clinical disorders are becoming an increasing public health burden. In this perspective, we postulate that impairment of microvascular function links obesity with insulin resistance and hypertension. Obesity is characterized by generalized microvascular dysfunction, which is associated with, and may precede, the development of insulin resistance and hypertension. Understanding of mechanisms involved in obesity-associated microvascular dysfunction may reveal new therapeutic targets. In obesity, cellular regulatory mechanisms of vasoreactivity are shifted towards vasoconstriction, with an increased role for endothelin-1 and a decreased role for nitric oxide. In addition, communicative pathways between adipose tissue and the microvasculature comprise increased release of adipokines and increased sympathetic activity. Although one mechanism may dominate, microvascular defects in obesity are probably caused by an integrated response consisting of endocrine, vasocrine and neurogenic mechanisms. This remains a fruitful area for future research.