Adipose tissue dysfunction rather than excess adipose tissue mass (defined as obesity) is mechanistically related to development of metabolic diseases traditionally linked to obesity: metabolic syndrome, type 2 diabetes and cardiovascular disease. Inflammation of adipose tissue seems to be an important manifestation of adipose tissue dysfunction and closely relates to insulin resistance, the mediator of obesity-related morbidity. However, it is not completely clear whether inflammation in adipose tissue leads to first, local, and then systemic insulin resistance or insulin resistance leads to adipose tissue inflammation, which, in turn, increases insulin resistance. These questions can only be answered by studying models of insulin resistance, independent of obesity. The conceptual shift from adipose tissue mass to adipose tissue function will have significant diagnostic and therapeutic implications. Our efforts in establishing markers to identify “at risk” population and finding newer therapeutic agents must focus on adipose tissue dysfunction and not on obesity alone.