Schizophrenia is a complex neuropsychiatric disease but, despite extensive research efforts over the last 100 years, the etiology of this disorder remains elusive. Diagnosis is still based on a subjective, interview-based process, which may not align with the biological underpinnings of the symptoms. This old-fashioned descriptive approach contributes to the low treatment success and impedes early intervention, which is thought to be crucial for successful therapy. Therefore, there is an urgent need to discover biochemical analytes that facilitate an objective and reliable diagnosis. Disease markers might also have utility for tracking treatment success and compliance, as well as the discovery of novel drug targets. For schizophrenia and psychiatric disorders at large, analyzing cerebrospinal fluid (CSF) is an intuitive choice due to its close proximity to the brain and its clinical accessibility in the living patient. Although numerous studies have aimed to identify potential diagnostic markers in the CSF of schizophrenia patients, as yet not one has found its way to clinical application. Here, we review molecular alterations of proteins and metabolites that have been identified in schizophrenia CSF and discuss their potential applicability as diagnostic markers.