There are many disorders of pyrimidine metabolism and those that involve an alteration in uridine metabolism have neurological and systemic effects, which provide insights into the biological activity of uridine and its analogues. Studies of the metabolism and actions of pyrimidines have uncovered a wealth of information on how these endogenous metabolites modulate cell physiology. In this article, the roles for the pyrimidine nucleoside uridine and its nucleotide derivatives in the regulation of a number of biological systems are examined and benefits of further studies are outlined. An understanding of how uridine and its nucleotides modulate such vastly complicated biological systems should ultimately lead to the development of new ways for modulating human physiology in both normal and diseased states. Likely targets for therapy include the respiratory, circulatory, reproductive, and nervous systems, and the treatment of cancer and HIV infection.