Visceral leishmaniasis, the most severe and potentially fatal form of leishmaniasis, is caused by the Leishmania donovani species complex. Matthew Berriman and colleagues report a high-quality reference genome sequence for a L. donovani strain from Nepal (Genome Res. published online, 28 October 2011; doi:10.1101/gr.123430.111). They also isolated and sequenced the genomes of 16 clinical strains from individuals in the same region with visceral leishmaniasis. The whole-genome sequence data set provides evidence of population structure beyond that detected using traditional multilocus typing, and there is evidence of adaptive evolution, including selection on genes with surface- and transport-related functions. Drug resistance was seen to emerge independently several times in the strains infecting this group of patients. In an accompanying paper, Jeremy Mottram and colleagues report a reference genome for L. mexicana and refine the three other Leishmania reference genomes (Genome Res. published online, 28 October 2011; doi:10.1101/gr.122945.111). Using comparative analyses, the authors identify a small number of genes and paralog groups unique to each of these species. They find high levels of gene copy-number variation between the species implicated in leishmaniasis. They also find that aneuploidy arises frequently, resulting in chromosome copy-number variation between leishmaniasis strains and species.