Over 30 million people in tropical regions suffer from Chagas disease, African sleeping sickness or leishmaniasis. The causative agents of these diseases, flagellated protozoa collectively known as kinetoplastids, represent an ancient lineage of eukaryotes. These unusual organisms carry out a large number of unique biochemical processes, one striking example being the sequence editing of mitochondrial messenger RNAs. In this review, Scott Seiwert focuses on recent studies that examine the reaction mechanism, molecular machinery and evolutionary history of this unusual RNA processing reaction.