Zinc Finger proteins (ZFs) are highly abundant eukaryotic proteins that play critical roles in transcription and translation. ZFs are cysteine rich proteins that utilize zinc as a co-factor. The role of zinc in ZFs has long been considered structural because Zn has a d10 metal center; however, we have obtained evidence that the ZF protein, tristetraprolin (TTP) can be modified by H2S via persulfidation of the cysteine residues that coordinate the Zn center. This modification requires Zn coordination and the presence of O2 suggesting that reactivity can occur at ZF sites. Persulfidation of cysteine residues is a new type of post translational modification, PTM, for which protein targets are not well defined. Our finding that TTP can be persulfidated suggests that ZF proteins may be a general site for ZF persulfidation. To test this hypothesis, we performed persulfide specific proteomics on mouse MEF and human THP cell lines and discovered ZF proteins are general sites for persulfidation. Subsequent meta analysis of all published persulfide specific proteomies data revealed that ZF persulfidation is common between species. We isolated a series of distinct ZF proteins, with different ligand sets, folds and functions, and determined that the ZFs all react with H2S to form persulfides and modulate function. The common feature for all of these ZF/H2S reactions is that Zn must be bound and O2 present. We proposed a mechanism in which Zn acts a conduit for electron transfer, and tested the mechanism using a Zn-coordination complex. These findings, along with current efforts to understand the link between ZF protein persulfidation, the pro-inflammatory response, and transcription and translation will be presented.