The incidence of candidemia and its complications, such as endophthalmitis, has measurably increased in recent years. However, the optimal method of treatment of hematogenous candidal infection remains a controversial issue. Traditional therapy with amphotericin B is associated with well-known adverse reactions. Many clinicians therefore prefer to use fluconazole, which is administered orally and is relatively less toxic. We recently observed a patient with candidal sepsis in whom blinding endophthalmitis developed despite aggressive and lengthy therapy with fluconazole. This grave clinical outcome and the data derived from experimental models of ocular candidal infection suggest that empirical usage of fluconazole may not be warranted in cases of disseminated candidiasis potentially complicated by endophthalmitis.