Candida albicans is an opportunistic pathogen that forms part of the commensal microbiota. After initial colonization, C. albicans adapts to environmental changes, particularly in response to stresses, such as antifungal treatment. For example, gain-of-function mutations in fungal transcription factors confer new phenotypes and are a common cause of antifungal resistance. In a recent study, Hampe et al. found that an acquired mechanism of antifungal resistance also enabled escape of host intrinsic immunity. Histatin 5, an antimicrobial peptide that is secreted in the saliva, has fungicidal activity against C. albicans. The authors observed that mutant Mrr1 (a transcription factor that upregulates the multidrug efflux pump MDR1 gene) strains also caused the overexpression of FLU1, a gene that encodes an efflux pump that confers histatin 5 resistance. This study demonstrates that antifungal therapy could promote the evolution of C. albicans strains that are resistant to host immune defences.