Human insulin and its related Insulin-like Growth Factor-I and II (IGFs) are small protein hormones that are key regulators of human metabolism, growth and life-span. Remarkably, insulin/IGF axis signaling is very conserved in all animal kingdom. 40 years after D Hodgkin pioneering work on insulin structure, the first insight into 3-D organization of human insulin:Insulin Receptor (IR) complex has been achieved. It revealed an unexpected mode of the hormone:receptor engagement, and explained/unified the wealth of accumulated biochemical data concerning insulin functionality. Moreover, extension of this work into insulin-related insects’ homologues confirmed structural and molecular basses of functional similarity between insect and human hormones. We have also been trying to address the issues related to (still unknown) storage form(s) of insulin in pancreas vesicles. Unexpectedly, this line of research linked insulin with its putative role in the Central Nervous System, and origins of this hormone in invertebrates. Highlights of all these aspects of insulin-based studies will be presented.