Here we review our recent crystallographic studies of glutathione S-transferases (GSTs) with a particular emphasis on human class pi and theta enzymes. We first determined the structure of human pi class GST in 1992. These studies have been extended to the structure determination of numerous enzyme complexes, which have revealed the intricate details of how substrates and inhibitors are bound to the enzyme and further details of the reaction mechanism. We have recently determined the first human theta class GST. This structure revealed a number of surprises including the existence of a sulfate binding pocket and a buried active site.