Obesity has become a very frequent condition with important consequences for the health of affected individuals. Current evidence shows that the excess of adipose tissue as observed in obesity is responsible for secreting inflammatory mediators in a deregulated manner, thus inducing a chronic state of systemic low-grade inflammation that underlies the metabolic and cardiovascular outcomes in these populations. This article reviews the state of the art regarding mediators produced in the adipose tissue, their roles in the pathophysiology of obesity-associated insulin resistance and diabetes, and finally, tries to build a bridge between these mechanistically oriented insights and clinical practice.