Childhood obesity is one of the most serious global public-health challenges of the twenty-first century. Over the past four decades, the number of children and adolescents with obesity has risen more than tenfold. Worldwide, an increasing number of youth are facing greater exposure to obesity throughout their lives, and this increase will contribute to the early development of type 2 diabetes, fatty liver and cardiovascular complications. Herein, we provide a brief overview of trends in the global shifts in, and environmental and genetic determinants of, childhood obesity. We then discuss recent progress in the elucidation of the central role of insulin resistance, the key element linking obesity and cardiovascular-risk-factor clustering, and the potential mechanisms through which ectopic lipid accumulation leads to insulin resistance and its associated cardiometabolic complications in obese adolescents. In the absence of effective prevention and intervention programs, childhood obesity will have severe public-health consequences for decades to come.