Two decades ago Fox and Woese demonstrated that the evolutionary comparison of 16/18S rRNA led to a trifucated unrooted tree that demonstrated that all living forms groups all living forms in one of three major phylogenetic lineages derived from a common ancestor. Bioinformatic analysis of completely sequenced cellular genomes from these three major kingdoms have been used to define the set of the most most conserved protein-encoding sequences to characterize the gene complement of of last common ancestor, or LUCA. Universal gene-based phylogenies ultimately reach a single universal ancestor, but it is now generally accepted that the term LUCA actually refers to an ancestral population. Attempts to reconstruct the LUCA gene complement are statistical approximations of biological past hindered by ancient horizontal gene transfer events, paralogous duplications and polyphyletic gene losses, as well as by biases in genome databases and methodological artifacts. A significant percentage of the highly conserved genes that may have been part of LUCA’s genome are sequences involved in the synthesis, degradation, and binding of RNA, including transcription and translation. Although the gene complement of LUCA includes sequences that may have originated in different epochs, the extraordinary conservation of RNA-related sequences supports the hypothesis that the last common ancestor was an evolutionary outcome of an earlier evolutionary stage during which RNA molecules and ribonucleotides played more conspicuous roles in genetic and metabolic processes.