SUMMARYA decade of genome sequencing has transformed our understanding of how trypanosomatid parasites have evolved and provided fresh impetus to explaining the origins of parasitism in the Kinetoplastida. In this review, I will consider the many ways in which genome sequences have influenced our view of genomic reduction in trypanosomatids; how species-specific genes, and the genomic domains they occupy, have illuminated the innovations in trypanosomatid genomes; and how comparative genomics has exposed the molecular mechanisms responsible for innovation and adaptation to a parasitic lifestyle.