Considerable advances have been made in insulin pharmacology and pharmacotherapeutics in the 77 years since its discovery by Frederick Banting and Charles Best at the University of Toronto. Nevertheless, even the most sophisticated regimens of diabetes management still do not replace insulin in a physiological manner, i.e. by portal secretion in precise amounts to respond to ingested nutrients and other secretogogues. It is for these reasons that insulin remains just one of many facets of optimal diabetes care. Further advances in the next few years can be expected to change some aspects of insulin therapeutics. However, in the absence of perfect physiological replacement, the goal of diabetes management remains the balancing of the different components of therapy in order to achieve the best possible metabolic control.