The incidence of invasive fungal diseases has increased over the past decades, particularly in relation with the increase of immunocompromised patient cohorts (e.g., HIV-infected patients, transplant recipients, immunosuppressed patients with cancer). Opportunistic fungal pathogens such as Candida spp. are most often associated with serious systemic infections. Currently available antifungal drugs are rather unspecific, often with severe side effects. In some cases, their prophylactic use has favored emergence of resistant fungal strains. Major antifungal drugs target the biosynthesis of lipid components of the fungal plasma membrane or the assembly of the cell wall. For a more specific and efficient treatment and prevention of fungal infection, new therapeutic strategies are needed, including strengthening or stimulation of the residual host immune response. Achieving such a goal requires a better understanding of factors important for the defense and the survival of the host combating Candida spp. Where possible, primary cultures of mammalian immune cells of the innate immune system constitute a better suited model than transformed cell lines to study host-pathogen response and virulence. Hence, in vitro primary cell culture systems are a good strategy for a first screening of mutant strains of Candida spp. to identify virulence traits with regard to host cell response and pathogen invasion.