Ribozymes and deoxyribozymes (collectively referred to as nucleic acid enzymes) can be designed to cleave substrate mRNAs in a sequence-specific manner, and thus represent a potentially important tool to inhibit selectively the expression of deleterious genes. Nucleic acid enzymes can be delivered to cells either as genes encoding RNA enzymes (ribozymes), or exogenously as in vitro produced agents. This review focuses in particular on the 'exogenous application' of ribozymes and deoxyribozymes as antiviral drugs. In the past few years, the therapeutic development of ribozymes and deoxyribozymes has encountered a variety of problems, several of which have now been solved thanks to a massive amount of research. Much progress has been made towards understanding the structure and mechanism of these catalysts, improving their stability and effectiveness in vivo, and investigating their clinical usage. Despite this, it is not yet clear whether these molecules can be developed into clinically useful pharmaceutical preparations. To address the long-term prospects of this class of therapeutics, it is necessary to consider their intrinsic capabilities and limits, the developmental difficulties that they still face and the comparative advantages and disadvantages they may offer with respect to other oligonucleotide-based therapeutic approaches.