Diabetes constitutes an increasing threat to human health, particularly in newly industrialized and densely populated countries. Type 1 and type 2 diabetes arise from different etiologies but lead to similar metabolic derangements constituted by an absolute or relative lack of insulin that results in elevated plasma glucose. In the last three decades, a set of new medicines built upon a deeper understanding of physiology and diabetic pathology have emerged to enhance the clinical management of the disease and related disorders. Recent insights into insulin-dependent and insulin-independent molecular events have accelerated the generation of a series of novel medicinal agents, which hold the promise for further advances in the management of diabetes. In this chapter, we provide a historical context for what has been accomplished to provide perspective for future research and novel emerging treatment options.