Hepatosplenic candidiasis (HSC) is an increasingly recognized complication of treatment with chemotherapeutic agents. The true incidence of HSC is not known, but most experts agree that there has been an increase in its occurrence during the past 15 years, and most of them attribute this rise to the use of more intensive chemotherapeutic regimens in the treatment of hematologic malignancies, especially, acute leukemia. The most recognizable risk factor predisposing for this complication is prolonged neutropenia. The diagnosis of HS requires high clinical suspicion and expertise in the interpretation of the histopathologic and radiologic data. Most importantly, treatment of the condition requires prolonged administration of antifungal drugs and continuous monitoring using combination of clinical, laboratory and radiologic tests in order to ascertain eradication of the infection. In this minireview I will present a summary of the data available in the literature in combination with our prospective experience in the investigation of HSC.