Adenosine to inosine RNA editing, catalyzed by Adenosine Deaminases Acting on RNA (ADARs), represents an evolutionary conserved post-transcriptional mechanism which harnesses RNA structures to produce proteins that are not literally encoded in the genome. The species-specific alteration of functionally important residues in a multitude of neuronal ion channels and pre-synaptic proteins through RNA editing has been shown to have profound importance for normal nervous system function in a wide range of invertebrate and vertebrate model organisms. ADARs have also been shown to regulate neuronal gene expression through a remarkable variety of disparate processes, including modulation of the RNAi pathway, the creation of alternative splice sites, and the abolition of stop codons. In addition, ADARs have recently been revealed to have a novel role in the primate lineage: the widespread editing of Alu elements, which comprise approximately 10% of the human genome. Thus, as well as enabling the cell-specific regulation of RNAi and selfish genetic elements, the unshackling of the proteome from the constraints of the genome through RNA editing may have been fundamental to the evolution of complex behavior.