Body composition is related to various physiological and pathological states. Characterization of individual body components adds to understand metabolic, endocrine and genetic data on obesity and obesity-related metabolic risks, e.g. insulin resistance. The obese phenotype is multifaceted and can be characterized by measures of body fat, leg fat, liver fat and skeletal muscle mass rather than by body mass index. The contribution of either whole body fat or fat distribution or individual fat depots to insulin resistance is moderate, but liver fat has a closer association with (hepatic) insulin resistance. Although liver fat is associated with visceral fat, its effect on insulin resistance is independent of visceral adipose tissue. In contrast to abdominal fat, appendicular or leg fat is inversely related to insulin resistance. The association between ‘high fat mass + low muscle mass’ (i.e. ‘sarcopenic adiposity’) and insulin resistance deserves further investigation and also attention in daily clinical practice. In addition to cross-sectional data, longitudinal assessment of body composition during controlled under- and overfeeding of normal-weight healthy young men shows that small decreases and increases in fat mass are associated with corresponding decreases and increases in insulin secretion as well as increases and decreases in insulin sensitivity. However, even under controlled conditions, there is a high intra- and inter-individual variance in the changes of (i) body composition; (ii) the ‘body composition–glucose metabolism relationship’ and (iii) glucose metabolism itself. Combining individual body components with their related functional aspects (e.g. the endocrine, metabolic and inflammatory profiles) will provide a suitable basis for future definitions of a ‘metabolically healthy body composition’.