In the immunocompromised patients, the main features of Chagas disease are severe clinical manifestations during the acute phase and reactivations occurring during the chronic phase. Reactivation is defined by a demonstration of trypomastigots on microscopic examination of blood or the identification of amastigots on biopsy samples and/or acute clinical manifestations during the chronic phase. In HIV patients, meningo-encephalitis and myocarditis are the major clinical syndromes of reactivation. In transplanted patients, cutaneous lesions often reveal the reactivation. A parasiticidal treatment (nifurtimox or benznidazole) should be initiated immediately. A secondary prophylaxis is indicated for HIV patients with CD4 cells count < 200/mm3. In the near future, quantitative PCR could allow to diagnose early reactivation, to initiate preemptive therapy and to closely monitor the therapeutic response. Due to the severe manifestations and prognosis of Chagas disease in the immunocompromised host, two serologic tests must be performed in the patient with an history of residency in endemic countries.