The standardization of antifungal sensitivity tests represents a huge advance in the detection of antifungal drug resistance. Thus, the reference methods of the European Committee on Antibiotic Susceptibility Testing and the Clinical Laboratory Standards Institute have proven capable of detecting strains of yeasts and filamentous fungi with high minimum inhibitory concentrations (MIC) to antifungal agents. This standardization has enabled the genetic alterations responsible for the high MICs to be studied at the molecular level. Furthermore, these strains have been used in experimental models to obtain pharmacokinetic parameters that may allow us to predict clinical response. However, the correlation of the course of the infection in humans with the sensitivity or resistance of the strain is a controversial area with many unanswered questions. We analyze whether the MICs of human pathogenic fungi have clinical relevance, that is, if they affect the course of the infection.