In diabetic disease, blood glucose, HbA1c and insulin levels qualify as biomarkers reflecting endocrine pancreas function, but their shortfall in being truly useful predictors or surrogate endpoints of "abnormal processes or disease" lies in that alteration in their levels are dependent on a variety comorbidities and occur too late in the disease process to be useful sentinels. Non invasive imaging of molecular targets within the beta cell carry the promise of revealing quantitative information about beta-cell mass that can, at least theoretically, be used to monitor, in real-time, the natural history of T1DM progression, assess novel therapies designed to drive the proliferation and differentiation of endogenous beta cell progenitors, appraise methods of preserving mature beta cell mass as well as to track the function and viability of transplanted cells and tissues. In this article, we review and deconstruct available information regarding the methodology of making non invasive measurements of VMAT2 in the pancreas and the validity of these measurements to estimate beta cell mass in vivo.