Data from the health survey for England 2006, showed that the prevalence of type 2 diabetes mellitus (T2DM) has more than doubled in men and women since 1991. In the USA certain States have a prevalence of T2DM of greater than 10%. Globally it has been reported that this increase is by no means slowing down and that the number of individuals with the disease is expected to rise from 171 million cases reported in 2000 to 366 million by the year 2030. Physical inactivity and obesity are two major risk factors for the development of T2DM. In this review we will discuss evidence of an association between physical inactivity, obesity and T2DM from prospective cohort studies and clinical trials. We will also discuss some of the potential mechanisms that are thought to link obesity and physical inactivity with the major pathophysiological precursor of T2DM, insulin resistance.