In 1929, Drury and Szent-Gyorgyi described the effects of a simple extract of heart muscle and other tissues on the mammalian heart. This extract was identified as adenylic acid and found to have profound effects on the cardiovascular system. The discovery and identification of adenyl purines and their effects on the cardiovascular system has now extended to other biological functions such as neurotransmission, neuromodulation, and endocrine/exocrine secretory functions and beyond. This review examines the history of the discovery and identification of the many roles played by adenyl purines in regulation of physiological homeostasis.