Small RNA molecules can participate in complex regulatory networks not merely through Watson-Crick interactions with other RNAs (as in anti-sense RNA), but also by forming discrete structures that bind protein or low-molecular weight targets. RNA aptamers derived from in vitro selections (SELEX) are being used inside cells for at least four purposes: (1) to antagonise normal cellular proteins as a means of elucidating their biological roles; (2) as decoys to natural RNA-binding proteins to reveal their functions or those of structural elements within naturally occurring transcripts; (3) as regulatory modules to govern the expression of exogenous genes; and (4) to antagonise disease-related targets for potential biomedical applications. This paper summarises recent advances in each of these areas, the parameters that influence successful application and the potential for future developments. The use of aptamers in vivo may serve as a paradigm for understanding how some non-coding RNAs and other elements of the ribonome exert their influence on the intracellular proteome, and is thus becoming an important tool for modern cell and molecular biology.