Many important cellular processes are regulated by small endogenous noncoding RNAs known as microRNAs (miRNAs). The precise molecular function of many miRNAs is unknown; different loss-of-function methods are required to gain insight into the biology of these small RNA molecules. Nucleic acid enzymes termed antagomirzymes are now shown to be valuable tools for the specific knockdown of miRNA in vitro and in vivo (see scheme).