Recently, mitochondria have been identified as an important contributor to virulence and drug tolerance of human fungal pathogens. In different scenarios, either hypo or hyper-virulence can result from changes to mitochondrial function. Similarly, specific mitochondrial mutations lead to either sensitivity or resistance to antifungal drugs. Here we provide a synthesis of this emerging field, proposing that mitochondrial function in membrane lipid homeostasis is the common denominator underlying the observed effects of mitochondria in drug tolerance (both sensitivity and resistance). We discuss how the contrasting effects of mitochondrial dysfunction on fungal drug tolerance and virulence could be explained, and the potential for targeting mitochondrial factors for future antifungal drug development.