The phenomenon of adenosine-to-inosine (A-to-I) RNA editing has attracted considerable attention from the scientific community due to its potential relationship to the evolution of cognition in animals. While A-to-I editing exists in all organisms with neurons, including those with primitive neuronal systems (hydra and nematodes), it is particularly frequent in organisms with a highly developed central nervous system (primates, especially humans). Diversification of RNA transcript sequences via A-to-I editing serves a number of different functional roles, such as altering the genome-templated identity of particular amino acids in proteins or altering splice site junctions and modulating regulation of alternatively spliced mRNA variants. Here we provide an overview of current computational and experimental methods for the high-throughput discovery of edited RNA nucleotides in the human transcriptome, as well as a survey of the existing RNA editing bioinformatics resources and an outlook of future perspectives.