Some Candida species are common commensals, which can become opportunistic pathogens in susceptible hosts. In severely ill patients, Candida species, particularly Candida albicans, can cause life-threatening systemic infections. These infections are difficult to diagnose, as symptoms are similar to those of systemic bacterial infections. These difficulties can lead to delays in initiation in antifungal therapy, which contributes to the high mortality rates (> 40%) associated with these infections. In order to investigate systemic Candida infection, mouse models have been developed that mimic human disease, the most common being the intravenous infection model and the gastrointestinal colonization and dissemination model. This review discusses the two models and the contributions that they have made to our understanding of fungal virulence, host response to infection and the development of novel antifungal therapies and diagnostics.