This is the first of four articles summarizing presentations at the seventh World Congress on the Insulin Resistance Syndrome, held in San Francisco, California, on 5–7 November 2009. This article pertains to cardiovascular disease (CVD) concepts. Yehuda Handelsman (Tarzania, CA), chair of the International Committee for Insulin Resistance, “revisited” the treatment of insulin resistance, discussing aspects of the metabolic findings of BARI-2D's insulin-sensitizing versus insulin-providing strategy comparison (1). “When it came to the control of glucose,” he said, “the group that was on sensitizers had a 0.5% improvement in A1C,” similar to that seen in PROactive (2). “We've seen [in RECORD (3) and ADOPT (4)],” he continued, “that if you are on sulfonylurea or metformin you lose control” whether on combination or single-agent treatment in comparison to the stability of glycemia with rosiglitazone. Furthermore, Handelsman pointed out that in BARI-2D, those undergoing CABG had better outcome with the insulin-sensitizing strategy. Reviewing the concept of metabolic syndrome, which has been defined and redefined many times since first proposed as Syndrome X by Reaven (5), Handelsman emphasized the potential benefit of thiazolidinediones, but suggested that the flawed Nissen metaanalysis of rosiglitazone (6) has led to the misperception that insulin resistance treatment is not of benefit. He asked, “Should we treat insulin resistance pharmacologically?” If there is little evidence that treatment of the syndrome is effective beyond the benefit of treatment of the components, then we may need more data to justify insulin sensitizer administration outside of diabetes treatment. It may, however, be the case that insulin levels per se can be used in guiding pharmacologic treatment, and Handelsman reviewed the evidence that pioglitazone did reduce CV event rates in subset analyses of PROactive. Insulin resistance treatment appears of benefit in the polycystic ovary syndrome (PCOS), and in nonalcoholic fatty liver disease (NAFLD), …