The discovery over 30 years ago that RNA molecules called ribozymes are able to catalyze chemical reactions was a breakthrough in biology. Because of their high specificity, wide range of target selection and action before protein translation, the different classes of both natural and artificial ribozymes have been claimed to be used as specific suppressors of gene functions with the additional aim of validating disease-related genes as potential targets for new therapeutic interventions. However, the lack of suitable delivery systems in to target cells still hampers the clinical development of ribozyme-based therapeutics. This review briefly summarizes the ever increasing evidence to the use of ribozymes as innovative nucleic acid-based enzymes along with their classifications, their mechanism in initiating catalytic effect, their design, delivery strategies and their potential pharmaceutical applications and their roles in gene function study and in target validation.