Candida albicans is one of the leading causes of hospital-acquired infections in immune compromised patients. The risk of both developing candidiasis and the clinical outcome of infection is variable among patients, and the host-dependent factors that contribute to patient susceptibility to C. albicans infection are poorly understood. In this issue of the Journal of Clinical Investigation, Michail Lionakis and colleagues at the National Institute of Allergy and Infectious Diseases demonstrated that the chemokine receptor CX3CR1 is required for the interaction of C. albicans and macrophages in the kidney. Mice lacking this receptor were prone to C. albicans-induced kidney failure; however, these mice did not have increased fungal burden in other organs. Furthermore, the authors found that patients with a mutation in the gene encoding CX3CR1 were at higher risk of candidiasis. This study identifies an important role for the interaction of C. albicans and macrophages in disease progression and outcome.