A comparative examination of the sequences and functions of molecules can reveal clues as to their origins. However, the unity of modern biochemistry makes it likely that most extant molecules descend from an organismal singularity known as the progenote, the last common ancestor of modern life. The progenote was already complex, containing a variety of enzymes and cofactors; multiple metabolic pathways; and replication, transcription, and translation apparatuses. Because nucleic acids and nucleic acid cofactors are prevalent in basal metabolic processes ranging from redox reactions to translation, one of the progenote’s predecessors has been hypothesized to have lived in an “RNA world” in which ribozymes, rather than protein enzymes, catalyzed most biochemical transformations. Further support for the existence of an RNA world has been garnered from the discovery of catalytic RNAs, and from experiments in which functional nucleic acids have been selected from random sequence populations. If functional nucleic acids or ribozymes are present in nature, or are relatively easy to generate by in vitro selection-the argument goes-then similar functional nucleic acids or ribozymes could have also existed during the evolution of an RNA world. In some cases though, these arguments are carried further, and it is claimed that, not only are natural or unnatural RNA molecules doppelgangers of ancient RNAs, but sequence or structural motifs that exist in modern RNA molecules are identical to those that existed in a putative RNA world. These claims should in all instances be evaluated in relation to the null hypothesis: that modern, functional RNAs may have arisen by chance and thus either This paper was originally presented at a workshop titled Evolution: A Molecular Point of View. The workshop, which was held at the Marine Biological Laboratory, Woods Hole, Massachusetts, from 24-26 October 1997, was sponsored by the Center for Advanced Studies in the Space Life Sciences at MBL and funded by the National Aeronautics and Space Administration under Cooperative Agreement NCC 2-896. have no historical connection to the RNA world, or at best have no connection that can be experimentally tested. Several popular vignettes of the RNA world, in which modern RNAs are claimed to descend from their forebears, will be examined in light of the null hypothesis.