The mitochondrion is generally considered to be a defining feature of eukaryotic cells, yet most anaerobic eukaryotes lack this organelle. Many of these were previously thought to derive from eukaryotes that diverged prior to acquisition of the organelle through endosymbiosis. It is now known that all extant eukaryotes are descended from an ancestor that had a mitochondrion and that in anaerobic eukaryotes the organelle has been modified into either hydrogenosomes, which continue to generate energy for the host cell, or mitosomes, which do not. These organelles have each arisen independently several times. Recent evidence suggests a shared derived characteristic that may be responsible for the retention of the organelles in the absence of the better-known mitochondrial functions--iron-sulfur cluster assembly. This review explores the events leading to this new understanding of mitochondrion-derived organelles in amitochondriate eukaryotes, the current state of our knowledge, and future areas for investigation.