The term rhombencephalitis refers to inflammatory diseases affecting the hindbrain (brainstem and cerebellum). Rhombencephalitis has a wide variety of etiologies, some of them potentially severe and life threatening without proper early treatment. In this retrospective observational study, we reviewed the records of consecutively hospitalized patients at University Hospital of Bellvitge (Barcelona, Spain) from January 1990 to December 2008. Rhombencephalitis was defined as a brainstem and/or cerebellar condition demonstrated clinically or by neuroimaging, with pleocytosis (>4 cells/mm) in cerebrospinal fluid. Ninety-seven patients (48 female; mean age, 37 yr; range, 14-79 yr) fulfilled these criteria. We reviewed their clinical, cerebrospinal fluid, and radiologic characteristics. The mean follow-up was 5 years (range, 0-20 yr). The etiologies of rhombencephalitis were as follows: unknown cause (n = 31), multiple sclerosis (n = 28), Behçet disease (n = 10), Listeria monocytogenes infection (n = 9), paraneoplastic syndrome (n = 6) (3 cases associated with anti-Yo antibodies and 3 with anti-Tr antibodies), Epstein-Barr virus (n = 4), tuberculosis (n = 2), pneumococcal infection (n = 2), systemic lupus erythematosus (n = 1), lymphoma (n = 1), Brucella species infection (n = 1), JC virus (n = 1), and relapsing polychondritis (n = 1). Certain clinical, cerebrospinal fluid, and radiologic characteristics that are commonly seen in some of these etiologies can guide us in the first approach to the etiologic diagnosis of rhombencephalitis.