Various stimuli have been used in clinical practice to test islet function, including intravenous glucose, arginine--both at basal glucose levels and with the hyperglycaemic clamp, tolbutamide, glucagon and glucagon-like peptide 1. The subsequent first phase insulin response (also termed acute insulin response or AIR) to intravenous glucose or arginine has been quantified in a variety of ways, from the mean serum insulin measured at multiple times after glucose injection to the mean value above baseline of serum insulin at 2 to 10 min. The purpose of this study was to review the different protocols of AIR calculation and their pitfalls, and to assess the results of AIR in the islet transplantation field. By investigating the first phase of insulin secretion, AIR provides both a qualitative and a quantitative approach to insulin secretion. In islet transplantation, post-glucose AIR (AIRg) may predict graft survival while post-arginine AIR (AIRa) may be better correlated with engrafted beta cell mass, despite these facts need to be confirmed. AIRa also limits intravenous hyperglycaemia glucotoxicity. In conclusion, AIR could help to predict the need for a second or third islet injection in islet transplantation. These specific indications, however, need to be confirmed by future studies and completed by other approaches such as insulin sensitivity studies and in vivo morphological assessment of islet mass.