Domino or cascade reactions involve the transformation of materials through several inseparable steps, which often proceed via highly reactive intermediates. In the case where the reaction sequence is triggered by a biocatalyst, such as an enzyme, the cascade may proceed in a highly chemo- or stereoselective way. In this review, emphasis is laid on biocatalyzed domino reactions of non-natural compounds (rather than natural substrates) which have been aptly denoted as ‘enzyme-initiated’ (or -‘triggered’) domino (or cascade) reactions. Biosynthetic pathways involving biological cascade reactions are out of the scope of this review (see, for example, D. E. Cane, Chem. Rev., 1990, 90, 1089).