Dendritic cells (DC) that express the type II C-type lectin DC-SIGN (CD209) are located in the submucosa of tissues, where they mediate HIV-1 entry. Interestingly, the pathogen Candidaalbicans, the major cause of hospital-acquired fungal infections, is found at similar sites. Here it is demonstrated that DC-SIGN is able to bind Candida albicans both in DC-SIGN transfected cell lines and in human monocyte derived DC. Moreover, in immature DC, DC-SIGN is able to internalize Candida in specific DC-SIGN enriched vesicles, distinct from those containing the mannose receptor (MR; CD206), which is another Candida receptor on DC. Together, these results demonstrate that C. albicans has two major receptors on human monocyte derived DC, these receptors being DC-SIGN and MR. Targeting of DC-SIGN offers novel opportunities to combat chronic forms of candidiasis.