Central nervous system (CNS) melioidosis is rare. However, delayed diagnosis and treatment could lead to fatality. To identify knowledge of CNS melioidosis, we systematically review case reports and case series.We searched through PubMed, Web of Science and Thai-Journal Citation Index databases as well as Google Scholar with the last date on July 10, 2018. The diagnosis of CNS melioidosis had to be confirmed with culture, serology or polymerase chain reaction. We excluded the animal cases and the studies that the clinical data were not available. We identified 1170 relevant studies, while 70 studies with a total of 120 patients were analyzed. Ninety-three percent of patients were reported from the endemic area of melioidosis. Median age was 40 years (IQR 18-53), and 70% were men. A total of 60% had one or more risk factors for melioidosis. The median duration from clinical onset to diagnosis was ten days (IQR 5-25). Fever (82%), headache (54%), unilateral weakness (57%) and cranial nerve deficits (52%) are among the prominent presentation. Most patient (67%) had at least one extraneurological organ involvement. The CSF profile mostly showed mononuclear pleocytosis (64%), high protein (93%) and normal glucose (66%). The rim-enhancing pattern (78%) is the most frequent neuroimaging finding in encephalomyelitis and brain abscess patients. Both brainstem (34%) and frontal lobe (34%) are the most affected locations. Mortality rate was 20%.This study is the most extensive systematic review of case reports and case series of CNS melioidosis in all age groups. However, the results should be cautiously interpreted due to the missing data issue. The propensity of brainstem involvement which correlates with prominent cranial nerve deficits is the characteristic of CNS melioidosis especially encephalomyelitis type. The presenting features of fever and neurological deficits (especially cranial nerve palsies) along with the mononuclear CSF pleocytosis in a patient who lives in the endemic area and also has the risk factor for melioidosis should raise the CNS melioidosis as the differential diagnosis.