Epithelial cells present an interface between potentially harmful microorganisms on the one side and innate immune cells on the other side. Therefore, their role is to tolerate commensal microbes and initiate host defense upon infection. The commensal lifestyle of Candida species on epithelial surfaces is finely conditioned by the bacterial microbiota and the immune system, but if these protective mechanisms are compromised, Candida spp. can undergo a commensal-to-pathogen shift and cause infection. In that case, fungal proliferation on the mucosal surfaces of the gut, oral cavity, or vagina, leads to epithelial damage and the initiation of pro-inflammatory immune responses. C. albicans, C. tropicalis, C. glabrata, and C. parapsilosis are responsible for more than 90% of Candida infections, but their pathogenicity strategies are remarkably different. Furthermore, each mucosal niche has unique properties, where both host and Candida spp. have to sense, adapt, and respond to the dynamics of specific microenvironments, depending on the nature of their host-pathogen interaction.