Trans-splicing is a recently discovered phenomenon defined as the splicing together of two discrete RNA molecules to give a single hybrid RNA product. There are two distinct types of physiological trans-splicing. The first is found in organelles of eukaryotes. Very little is known of the mechanism or machinery involved in this process but so far it bears little resemblance to the cis-splicing of nuclear-encoded mRNAs (in terms of the sequences involved). The second process occurs in the nucleus of eukaryotic cells and is clearly related to the well-studied cis-splicing occurring on spliceosomes in these nuclei. “Nuclear” trans-splicing will be the major focus of this review. In it, I will attempt to cover the structures involved, as well as the possible mechanism, function and evolutionary significance of this unusual but important process.