1. Ribozymes can be designed to cleave in trans, i.e. several substrate molecules can be turned over by one molecule of the catalytic RNA. Only small molecular weight ribozymes, or small ribozymes, are discussed in this review with particular emphasis on the hammerhead ribozyme as this has been most widely used for the inhibition of gene expression by cleavage of mRNAs. 2. Cellular delivery of the ribozyme is of crucial importance for the success of inhibition of gene expression by this methodology. Two modes of delivery can be envisaged, endogenous and exogenous delivery. Of the former several variants exist, depending on the vector used. The latter is still in its infancy, even though chemical modification has rendered such ribozymes resistant against degradation by serum nucleases without impairment of catalytic efficiency. 3. Various successful applications of ribozymes for the inhibition of gene expression are discussed, with particular emphasis on HIV1 and cancer targets. These examples demonstrate the promise of this methodology.