A secretome signature is a heterogeneous profile of secretions present in a single cell type. From the secretome signature a smaller panel of proteins, namely a secretion fingerprint, can be chosen to feasibly monitor specific cellular activity. Based on a thorough appraisal of the literature, this review explores the possibility of defining and using a secretion fingerprint to gauge the functionality of pancreatic islets of Langerhans. It covers the state of the art regarding microfluidic perfusion systems used in pancreatic islet research. Candidate analytical tools to be integrated within microfluidic perfusion systems for dynamic secretory fingerprint monitoring were identified. These analytical tools include patch clamp, amperometry/voltametry, impedance spectroscopy, field effect transistors and surface plasmon resonance. Coupled with these tools, microfluidic devices can ultimately find applications in determining islet quality for transplantation, islet regeneration and drug screening of therapeutic agents for the treatment of diabetes.