In vitro selection and in vitro evolution methods represent powerful tools for isolating functional RNA molecules, and are proving to have wide applications in biology. Selection in the absence of living cells is possible because some RNA molecules possess a selectable "phenotype" (catalytic activity or ligand binding) as well as a "genotype" (nucleotide sequence). This review discusses the basic principles of in vitro selection technology and the application of these methods to isolate RNA molecules with interesting and novel properties. Selection techniques have been used to analyze the structure and function of catalytic RNA molecules (ribozymes), and to isolate novel catalytic structures not found in nature. They are also useful for studying protein-RNA interactions and for isolating RNA molecules that bind specifically to peptides and other ligands. The isolation of RNA molecules with new binding functionalities (aptamers) for both large and small molecules has exciting potential for discovery of new drugs and diagnostic reagents.