In this issue of the Journal, Bucşan and colleagues (pp. 94–104) present an extensive comparative analysis of two widely used, virulent strains of Mycobacterium tuberculosis (Mtb) in the nonhuman primate (NHP) model (1). They found that the Erdman strain was considerably more virulent than the CDC1551 strain by multiple parameters: larger areas of necrotic granulomas, poorer survival, increased bacterial lung burden, increased lung pathology associated with greater systemic inflammation, and a high and early inflammatory myeloid cell influx to the lung with evidence of greater macrophage and T-cell activity in the lung. Comparison of gene expression signatures in the lungs of infected animals by RNA sequencing revealed that pathways associated with the hypoxia response and lung tissue remodeling were induced to higher degrees in Erdman-infected animals.