Isoprenoids comprise a family of more than 23,000 natural products, among them the precursors of cholesterol and taxol. The structures of three isoprenoid-cyclizing enzymes have recently been determined and here are placed in the greater context of isoprenoid biosynthesis. On the basis of reaction mechanisms, a subdivision into class I and class II enzymes is proposed. The chain folds of these enzymes also appear to fall into the same two distinct classes, suggesting that class I and class II enzymes have evolved separately.