RAS activation has been related to both insulin resistance and β-cell dysfunction [24–27]. As such, in rodents, the presence of hyperglycaemia increased expression of RAS components, including AngII, in pancreatic islets, adipose tissue and skeletal muscle [28,29]. Furthermore, AngII diminished insulin secretion in pancreatic β-cells  and impaired insulin sensitivity in adipose and skeletal muscle tissue [31–33]. In large clinical trials blockade of RAS with an ACEi or ARB delayed the onset of T2DM in subjects with hypertension [34–36]. On the basis of multiple meta-analyses, it is suggested that treatment with an ACEi or ARB reduces the incidence of T2DM by 22–30% [13,37]. However, in most of the trials investigating the effect of RAS blockade on the incidence of T2DM, the onset of T2DM was not a prespecified endpoint. Recently, two large-scale prospective trials (the Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication, DREAM trial  and the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research, NAVIGATOR trial ) specifically addressed the potential of the ACEi ramipril and the ARB valsartan, respectively, on incident T2DM in normotensive individuals with IGM. In the DREAM trial, ramipril (15 mg QD), given for 3 years, non-significantly reduced the incidence of T2DM by 9%. At 3 years, individuals treated with ramipril were more likely to revert from impaired to normal glucose metabolism (hazard ratio, 1.16; 95% CI: 1.07–1.27; p = 0.001) and their post-load glucose levels were significantly reduced compared to placebo (7.50 vs. 7.80 mmol/l, ramipril vs. placebo, respectively, p = 0.01) . In the NAVIGATOR trial, valsartan (160 mg QD), given for 5 years, not only reduced fasting and post-load glucose after an oral glucose tolerance test (OGTT), but also reduced the incidence of T2DM by 14% (p < 0.001) . As valsartan was given in addition to lifestyle modification, its true protective potential regarding the incidence of T2DM might be an underestimation. However, the underlying mechanisms are incompletely understood. Here, we discuss the possible effects of RAS blockade on β-cell function and insulin sensitivity. Meta-analyses, including 10 randomized controlled trials, could not establish differences in the beneficial effect of RAS blockade on onset T2DM between ACEi and ARB. Furthermore, as there are no head-to-head comparison studies comparing the effect of ACEi with that of ARB on β-cell function and insulin sensitivity, in this review data from studies investigating the effect of ACEi as well as ARB on glucose metabolism are described.