T here is overall agreement in the scientific and clinical community that obesity is one of the major public health problems of this century. The first documented reports on obesity date from the end of the 19th century and the beginning of the 20th century.1-3 From these days to date, >57 000 articles have been published in PubMed including the term obesity in the title, with these figures being 3× larger when searching by obesity also in the abstract. Figure 1 graphically Abstract: The prevalence of obesity has increased worldwide over the past few decades. In 2013, the prevalence of obesity exceeded the 50% of the adult population in some countries from Oceania, North Africa, and Middle East. Lower but still alarmingly high prevalence was observed in North America (≈30%) and in Western Europe (≈20%). These figures are of serious concern because of the strong link between obesity and disease. In the present review, we summarize the current evidence on the relationship of obesity with cardiovascular disease (CVD), discussing how both the degree and the duration of obesity affect CVD. Although in the general population, obesity and, especially, severe obesity are consistently and strongly related with higher risk of CVD incidence and mortality, the one-sizefits-all approach should not be used with obesity. There are relevant factors largely affecting the CVD prognosis of obese individuals. In this context, we thoroughly discuss important concepts such as the fat-but-fit paradigm, the metabolically healthy but obese (MHO) phenotype and the obesity paradox in patients with CVD. About the MHO phenotype and its CVD prognosis, available data have provided mixed findings, what could be partially because of the adjustment or not for key confounders such as cardiorespiratory fitness, and to the lack of consensus on the MHO definition. In the present review, we propose a scientifically based harmonized definition of MHO, which will hopefully contribute to more comparable data in the future and a better understanding on the MHO subgroup and its CVD prognosis. (Circ Res.