This article sets out the clinical context of the research presented by Romero-Corral et al. in an accompanying article in this journal. Obesity is an important risk factor for the development of cardiovascular disease. Among other metabolic abnormalities, obesity is associated with elevated levels of the inflammatory biomarker C-reactive protein (CRP) and of leptin. Here, we discuss the study carried out by Romero-Corral and colleagues-an analysis of leptin, CRP and cardiovascular risk factors. These researchers found that raised leptin concentrations were a more robust predictor of cardiovascular events than CRP; the highest risk was observed in participants with raised concentrations of both markers. We explore the possible mechanism for this interaction, and propose that leptin's stimulatory effect on the sympathetic nervous system and its ability to impair baroreceptor control might be involved.