The plasma membrane is critical for the survival of fungal pathogens in the host because this protective barrier also mediates a wide array of dynamic functions including nutrient uptake, secretion, endocytosis, morphogenesis, cell wall synthesis, and stress resistance. Studies aimed at defining how cells coordinate these diverse functions have shown that the plasma membrane is organized into distinct compartments that vary in size, shape, and stability. Interestingly, a novel type of membrane domain was discovered in yeast that is termed the MCC/eisosome. These domains are distinctive in that they are protein-organized structures that correspond to stable furrows in the plasma membrane. In the human fungal pathogen Candida albicans, mutants that fail to form MCC/eisosomes (pil1 lsp1) display broad abnormalities including defects in cell wall synthesis, polarized morphogenesis, and invasive growth. In addition, MCC/eisosome mutants are more susceptible to a variety of stresses encountered in vivo, such as elevated temperature, oxidation, copper and antifungal drugs. Genetic analysis indicates that proteins recruited to the MCC/eisosomes, such as Sur7, Nce102, Pst1, Pst2, Pst3, and Ycp4, promote the proper regulation of cell wall synthesis and stress responses. Consistent with this, mutants lacking these MCC/eisosome proteins are defective in virulence. Thus, studies on MCC/eisosomes are defining novel plasma membrane functions that will help to identify new targets for antifungal therapy.