Biology capitalizes on the specific chemistries of certain transition metal ions. In fact, life depends on transition metal ions as essential trace elements. Biological redox processes, such as nitrogen fixation, photosynthesis, and mitochondrial respiration, rely on the chemistries of molybdenum, iron, manganese, and copper. Zinc (Zn2+) is first among equals in the series of biologically important transition metals. In thousands of proteins, zinc participates in enzymatic catalysis, structural organization, and/or regulation of function. The great number and variety of zinc proteins has stimulated research on the zinc regulatory and chemical mechanisms that safeguard distribution of zinc to proteins within the cell in a timely and spatially coordinated manner. Zinc concentrations inside cells are strictly controlled to fulfill all the biological function of zinc in proteins and to avoid unwanted side effect of excess zinc ions, such as their influence on the misfolding and aggregation of proteins (Figure 1). Regulatory roles of zinc require transient binding. Therefore, the commonly held view of zinc sites in proteins as permanent fixtures is beginning to change. Many functions of zinc in proteins also require dynamic structures. The usual description of zinc coordination environments as being static neglects a fundamental functional potential of zinc in biology. In this review, we will address the dynamics of zinc coordination and the cellular distribution of zinc, namely, how proteins control zinc (zinc metalloregulation), how zinc controls proteins (zinc signaling), and how zinc concentrations are regulated and buffered intracellularly. The chemical properties of zinc in enzymes are largely attributed to its function as a relatively strong Lewis acid. 1 Generally, fast ligand exchange, stereochemical flexibility, and redox-inertness are additional characteristics for the selection of zinc ions in the function of so many proteins. Its physical properties render zinc invisible to most spectroscopic methods of investigation, precluding the application of many techniques that have been instrumental in understanding the functions of other transition metal ions. The coordination spheres in zinc proteins have been probed with various spectroscopies of metal-substituted zinc enzymes, especially cobalt (II), which serves best as a probe, because its coordination is virtually isostructural with that of zinc and it retains catalytic activity while probing metaldependent steps in the mechanisms of enzymes. 2 However,