Diabetes, and especially the predominating Type 2 form, has reached epidemic proportions worldwide, with a predicted 30–50% increase in prevalence over the few next decades [101]. The pancreatic β-cells, which produce insulin in the pancreatic islets of Langerhans play a central role in the pathogenesis of most forms of the disease. Still, numerous questions about the natural history of diabetes remain unanswered, mostly due to the lack of noninvasive methods, which can be used to repeatedly monitor β-cell mass and function in vivo. Also, the available treatments are not curative, nor do they prevent the long-term clinical complications that result from the chronic hyperglycemia and metabolic alterations due to the altered balance between the islet hormones, notably insulin and glucagon. Presently, the efficacy of novel candidate therapies cannot be directly evaluated in vivo by repeated monitoring of the same animal and, a fortiori, the very same patient. Noninvasive imaging could be instrumental to address these key unanswered questions. Still, the imaging of native islets, and specifically of β-cells, within the in situ pancreas remains a sizable challenge, owing to a number of anatomical, cellular and physiological factors which converge to complicate image acquisition and analysis. Thus, several different methods are being investigated to determine which approach, or combination thereof, capable of sufficient tissue penetration to reach the human pancreas in the native abdominal location, could provide a sufficient resolution and fast operating acquisition to visualize individual islets of Langerhans. The ideal method(s) should provide for sound quantitative estimates of both the β-cell mass (presumably altered in most forms of diabetes) and function (largely affected in the residual β-cells of the most frequent Type 2 diabetes, and in the rare patients with a form of maturity onset diabetes of the young). Several American and European initiatives have been launched towards the development of such methods, including the Use of Innovative Strategies for b-cell Imaging in Diabetes Mellitus (BetaImage) project [102], which was initiated at the end of 2008 in the seventh Framework EU Program HEALTH. The EANM meeting [103] brought together four partners of this project and a collaborating clinician to discuss the advances and problems of the noninvasive imaging of pancreatic β-cells.