Between 70 and 80% of Valley fever patients receive one or more rounds of antibiotic treatment prior to accurate diagnosis with coccidioidomycosis. Antibiotic treatment and infection (bacterial, viral, fungal, parasitic) often have negative implications on host microbial dysbiosis, immunological responses, and disease outcome. These perturbations have focused on the impact of gut dysbiosis on pulmonary disease instead of the implications of direct lung dysbiosis. However, recent work highlights a need to establish the direct effects of the lung microbiota on infection outcome. Cystic fibrosis, chronic obstructive pulmonary disease, COVID-19, andM. tuberculosisstudies suggest that surveying the lung microbiota composition can serve as a predictive factor of disease severity and could inform treatment options. In addition to traditional treatment options, probiotics can reverse perturbation-induced repercussions on disease outcomes. The purpose of this review is to speculate on the effects perturbations of the host microbiome can have on coccidioidomycosis progression. To do this, parallels are drawn to aa compilation of other host microbiome infection studies.