The roles of zinc in biology are often thought to be limited to activating water, as in hydrolytic enzymes, and conferring structure, as in the zinc finger proteins. Over the past 15 years, it has been shown that there are many zinc-containing proteins that have 'structural-like' zinc sites with multiple cysteine ligands but in which the site promotes the alkylation of a zinc-bound thiolate. Recent work continues to extend the range of proteins showing zinc-promoted alkytransfer activity, and has refined the structural details of these sites. Of particular interest are recent crystal structures suggesting that in most cases the endogenous ligand that is displaced when the substrate thiol bind is an endogenous amino acid and not water, as had been previously thought. Despite extensive study, it remains unclear whether these enzymes function via an associative mechanism (direct alkylation of a zinc-bound thiolate) or a dissociate mechanism (nucleophilic attack by a free thiolate that has dissociated from the zinc).