In the past five years, with the use of molecular strategies the phylogenetic affinities of the two more resilient pathogens studied in medical mycology, Lacazia loboi and Rhinosporidium seeberi were finally deciphered. These studies found that L. loboi was the sister taxon to Paraccidioides brasiliensis, and R. seeberi was closely related to protistan spherical aquatic fish pathogens, located at the point were animals diverged from the fungi, in the class Mesomycetozoea. These initial studies indicated that a molecular strategy was the ideal approach to further understand these anomalous pathogens. However, the limited amount of information gathered so far from few DNA sequences, although crucial to place these organisms in the tree of life and to take a glance to their ecological preferences, did not provide answers to other important traits. In the following pages we discuss a genomic perspective for both pathogens and the benefit that such information could generate to understand more about these two uncultivated pathogens.