The majority of cellular zinc is tightly bound to proteins, where it has either catalytic or structural functions. Nevertheless, a regulatory role for zinc also exists, which is mediated by the small fraction of free or loosely bound zinc. This chapter discusses the role of free zinc in signal transduction. Different types of zinc signals were observed in eukaryotic cells, ranging from fast changes in less than a minute to signals that accompany cellular differentiation and last for several days. A range of molecular targets for these zinc signals has been identified, including a regulation of the activity of several kinases, phosphatases, phosphodiesterases, caspases, and transcription factors.