The Trypanosomatidae is closely related to euglenids that harbor plastids acquired from a green alga via secondary endosymbiosis. This discovery led to the idea that trypanosomatid parasites contained a green alga–derived plastid in their evolutionary past, an evolutionary scenario that was criticized based on the rarity of plant/plastid/cyanobacterium-like genes in the completely sequenced genomes of Trypanosoma and Leishmania species. Because it is difficult to identify such genes, however, their apparent rarity does not preclude a previous plastid endosymbiosis in the Trypanosomatidae. The genome of the plastid-less apicomplexan Cryptosporidium parvum preserves only a handful of plant/plastid/cyanobacterium-like genes, suggesting massive loss of plastid genes after elimination of its plastid. Additional support for such wholesale gene loss comes from fucoxanthin-containing dinoflagellates. Trypanosomatid nuclear genomes contain cyanobacterium-, green plant–, and haptophyte alga–derived genes, suggesting that they could have possessed a plastid in their evolutionary past; however, these genes also could represent examples of more typical horizontal gene transfer that did not accompany a plastid endosymbiosis. Thus, the presence of host cell genes that were adapted for use in the plastid would be much stronger evidence for a past plastid endosymbiosis in the Trypanosomatidae. Good examples of such genes are those encoding superoxide dismutases (SODs). Trypanosomatid parasites possess 4 iron-containing SODs, with 2 of them, SODA and SODC, targeted to the mitochondrion. In contrast with SODAs with classical single-domain mitochondrial targeting signals, SODCs carry bipartite pre-sequences composed of a signal peptide, followed by a transit peptide. Interestingly, these N-terminal extensions show striking similarities in length, hydropathy profiles, amino acid composition, and targeting properties to pre-sequences of proteins targeted to eukaryotic alga–derived plastids of euglenids and dinoflagellates. In turn, phylogenetic analyses indicate that SODCs originated from a mitochondrion-targeted SOD via gene duplication and were inherited vertically in the trypanosomatid lineage. These data represent a new kind of evidence for a past plastid endosymbiosis in the Trypanosomatidae, but the nature of this plastid remains unclear. It is usually assumed that the trypanosomatid plastid shared a common origin with that of euglenids, but Δ4 desaturase phylogenies suggest that it could have originated via an independent, tertiary endosymbiosis involving a haptophyte alga. It is also possible that ancestors of the Trypanosomatidae initially possessed a primary plastid that later was replaced by a secondary or tertiary plastid.