The development of an artificial pancreas for the treatment of insulin-dependent diabetes is a highly desired endeavor for patients, physicians, scientists, and engineers. Historical algorithms and recent progress in research and technology are reviewed in the present article, together with aspects of beta-cell physiology that lead to normal glucose tolerance. Algorithms are evaluated for their ability to deliver insulin as to recreate, as closely as possible, glucose and insulin profiles observed in healthy individuals. Emphasis is placed upon how the algorithms compare to the beta-cell's secretory response, specifically first-phase and second-phase insulin secretion. Experimental closed-loop data employing intravenous and subcutaneous glucose sensors and implanted and external insulin pumps (Medtronic MiniMed, Northridge CA) are presented.