Genomes of pathogenic bacteria evolve by large-scale changes in gene inventory. The continual acquisition of genomic islands, which refines their metabolic arsenal, is offset by gene loss. Far from this being a passive deletion of genes no longer useful to pathogens, the removal of genes encoding problematic metabolic process and immunogenic surface antigens might be strongly beneficial. Genomes of virulent eukaryotes show the footprint of similar genomic alterations, including acquisition of genes by lateral transfer, and genome degradation in obligate pathogens. These common features suggest that unicellular pathogens share common strategies for adaptation.