Candida albicans asymptomatically colonizes healthy individuals, but it is also an opportunistic pathogen that can translocate across the intestinal epithelium and cause bloodstream infections. Using in vitro cell culture models, Allert, Förster et al. show that translocation through an intact intestinal barrier is initiated by invasion and followed by cellular damage and loss of epithelial integrity. Translocation occurs mainly via a transcellular route, which causes necrotic epithelial damage. The cytolytic peptide toxin of C. albicans, candidalysin, was found to be essential for damage of enterocytes and was a key factor in fungal translocation. However, fungal invasion and low-level translocation can also occur in a candidalysin-independent manner — possibly by passing through intercellular spaces.