Thymidylate synthase plays a central role in the biosynthesis of thymidylate, an essential precursor for DNA biosynthesis. In addition to its role in catalysis and cellular metabolism, it is now appreciated that thymidylate synthase functions as an RNA binding protein. Specifically, thymidylate synthase binds with high affinity to its own mRNA, resulting in translational repression. An extensive series of experiments has been performed to elucidate the molecular elements underlying the interaction between thymidylate synthase and its own mRNA. In addition to characterization of the underlying cis- and trans-acting elements, recent studies have shown that thymidylate synthase has the capacity to bind specifically to other cellular RNA species. While the biological significance of these other RNA/thymidylate synthase interactions remains to be defined, this work suggests a potential role for TS in coordinately regulating several critical aspects of cellular metabolism.