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Candida albicans is the most prevalent human fungal pathogen, with an ability to inhabit diverse host niches and cause disease in both immunocompetent and immunocompromised individuals. C. albicans also readily forms biofilms on indwelling medical devices and mucosal tissues, which serve as an infectious reservoir that is difficult to eradicate, and can lead to lethal systemic infections. Biofilm formation occurs within a complex milieu of host factors and other members of the human microbiota. Polymicrobial interactions will probably dictate the cellular and biochemical composition of the biofilm, as well as influence clinically relevant outcomes, such as drug and host resistance and virulence. In this manuscript, we review C. albicans infections in the context of in vivo polymicrobial biofilms and implications for pathogenesis.