The ongoing obesity epidemic places about a third of American youth at risk for developing obesity-related insulin resistance. This is manifested by reduced multiorgan effects of insulin, leading to elevated insulin concentrations and, in some cases, inappropriately elevated glucose and lipid concentrations. Many risk factors for insulin resistance—including genetics, epigenetics, obesity, diet, and lifestyle—are in common between adolescents and adults. However, adolescents have a unique risk factor in the physiologic insulin resistance of puberty, which along with obesity can pose a “double hit” to the beta-cell, causing increased burden for insulin secretion. The diagnosis of insulin resistance-related health conditions is more difficult in pediatric patients, due to physiological growth and change that makes the establishment of standards difficult. Such conditions include nonalcoholic fatty liver disease, polycystic ovary syndrome, metabolic syndrome, prediabetes, type 2 diabetes, and lipodystrophies, each of which would obligate additional screening or treatment. Research on treatment options generally addresses holistic changes in diet and lifestyle, with or without the addition of insulin sensitizers. Though these interventions require diligence and can be difficult to maintain, even small successes can create improvements to measured insulin resistance.