For decades, the link between increased body fat and insulin resistance has been recognized. So, why a whole chapter on a simple, well-established concept? Perhaps because this topic is not as crystal clear as it appears at first glance. It was once thought that declining insulin sensitivity was associated with age — the older you get, the more insulin resistant you become. However, since the advent of advanced imaging techniques in the 1980s and 90s, it has become apparent that insulin resistance is actually associated with the increase in body fatness that occurs during aging, rather than aging per se. In addition, these imaging techniques have fuelled the debate about which regional adipose depot — total body fat, subcutaneous fat, visceral fat, or deep subcutaneous fat — contributes most significantly to insulin resistance. This debate, in turn, has spurred investigation into the mechanism(s) behind the detrimental effect of body fat on insulin sensitivity. Finally, we are faced with the “chicken and egg” scenario: which comes first, increased adiposity or deteriorating insulin sensitivity? Superimposed on these issues is the confounding effect of the many different methods used to assess insulin sensitivity and body composition by different investigators. So, the goal of this chapter will be to unravel some of the literature dedicated to assessing the effect of body composition on insulin sensitivity and to track the effect of body fat on insulin sensitivity through the human lifespan — from childhood precursors to adult disease. The focus will be on the most recent literature, with the data on childhood and adolescence taking prominence, as other texts have comprehensively reviewed the adult literature in the past.