Trypanosoma cruzi, a protozoan parasite and the causative agent of Chagas disease, is capable of inducing meningoencephalitis. Independent of the progression from acute to chronic myocarditis observed in immunocompetent T. cruzi-infected patients, inflammation of the central nervous system (CNS) self-resolves during acute infection. In contrast, in chronically infected immunocompromised Chagas disease patients, the CNS is a major site of reactivation, which can lead to severe and frequently fatal meningoencephalitis. More than one hundred years after the discovery of Chagas disease, many questions concerning the molecular mechanisms involved in the induction and resolution of T. cruzi-provoked meningoencephalitis remain unanswered. The study of murine models that reproduce crucial aspects of T. cruzi-elicited CNS inflammation has not only shed light on some of these questions, but it has also raised additional ones. Here, we discuss our results in the context of the current literature, questioning the involvement of CNS alterations caused by the inflammation and parasite in the behavioral abnormalities observed during T. cruzi infection.