The possibility of evolving a commonly existing biomolecule into a variety of functional biomolecules has now been realized in the form of aptamers through the development of in vitro selection. In addition to their high affinity and high specificity for the desired targets, aptamers are easily synthesized chemically and can be modified for downstream applications. Although aptamers were originally selected from a library containing only natural components, the past decade has seen a wealth of new aptamers selected from libraries containing unnatural components to provide new aptamer functions artificially. In this review, we highlight this transition (the shift between selection from natural components and selection from unnatural components) and the applications of selected aptamers.