Glycine encephalopathy (GCE) is an autosomal recessive error of glycine degradation, resulting in a poor outcome with severe mental retardation, intractable seizures and spasticity. Milder variants with a significantly better outcome have been reported, but an early prediction of the long-term outcome is not yet possible. With regard to the long-term outcome, the data reported in the literature of children with different GCE forms were compared. Determination of cerebrospinal fluid and plasma glycine concentrations at the time of diagnosis were not useful in differentiating mild and severe outcomes. By contrast, several clinical parameters correlate with a poor outcome: spastic quadriparesis, truncal hypotonia, typical electroencephalography patterns, congenital and cerebral malformations (e.g., corpus callosum hypoplasia). Hyperactivity, behavioral problems and choreiform movement disorders are associated with a milder outcome. Thus, prediction of the outcome of GCE may be facilitated by searching for selected clinical parameters. In addition, early neuroimaging may be a valuable tool in predicting the outcome of GCE.