We present a case of chagasic meningoencephalitis reactivation in an HIV-infected woman with advanced immunosuppression. Prolonged survival was attained with antiparasitic therapy and secondary prophylaxis, in conjunction with the use of highly-active antiretroviral therapy. The geographic expansion of the HIV epidemic around the world coupled with global migration and international travel have created a favourable situation for Trypanosoma cruzi and HIV coinfection. The clinical manifestations of Chagas disease in HIV-positive people usually represent reactivation and not acute infection with T cruzi (coinfection). Symptomatic reactivation of chronic latent T cruzi infection can be triggered by severe immunosuppression associated with HIV infection. In this setting, Chagas disease reactivation often presents as meningoencephalitis resembling toxoplasma encephalitis. We review, in this Grand Round, the clinical manifestations, diagnostic approach, pathogenesis, natural history, treatment, prognosis, and prevention of Chagas disease reactivation among HIV-infected people with an emphasis on CNS manifestations.