Valley fever is a respiratory disease caused by a soil fungus,Coccidioides, that is inhaled upon soil disruption. One mechanism by which the host immune system attempts to control and eliminateCoccidioidesis through granuloma formation. However, very little is known about granulomas duringCoccidioidesinfection. Granulomas were first identified in tuberculosis (TB) lungs as early as 1679, and yet many gaps in our understanding of granuloma formation, maintenance, and regulation remain. Granulomas are best defined in TB, providing clues that may be leveraged to understandCoccidioidesinfections. Granulomas also form during several other infectious and spontaneous diseases including sarcoidosis, chronic granulomatous disease (CGD), and others. This review explores our current understanding of granulomas, as well as potential mechanisms, and applies this knowledge to unraveling coccidioidomycosis granulomas.