Changes in diagnostic criteria have impacted on the definition of the metabolic syndrome. The central aetiological importance of insulin resistance has lessened, while the role of other cardiovascular risk factors has progressively increased. Inflammatory mediators have also been identified as crucial targets for more selective therapies in metabolic syndrome. Among several pro-inflammatory factors, adiponectin has been shown to be associated with reduced cardiovascular risk in metabolic syndrome patients. Here, we review new therapeutic approaches, which could potentially increase adiponectin levels in metabolic syndrome.