Meningoencephalitides of Unknown Origin (MUO) comprises a group of non-infectious inflammatory brain conditions, which frequently cause severe neurological disease and death in dogs. Although multiple diagnostic markers have been investigated, a conclusive diagnosis, at present, essentially relies on postmortem histopathology. However, different groups of biomarkers, e.g. acute phase proteins, antibodies, cytokines, and neuro-imaging markers may prove useful in the diagnostic investigation of dogs with MUO. It appears from the current literature that acute phase proteins such as C-reactive protein are often normal in MUO, but may be useful to rule out steroid responsive meningitis-arteritis as well as other systemic inflammatory conditions. In antibody research, anti-glial fibrillary acidic protein (GFAP) may play a role, but further research is needed to establish this as a consistent marker of particularly Pug dog encephalitis. The proposed diagnostic markers often lack specificity to distinguish between the subtypes of MUO, but an increased expression of interferon-γ (IFN-γ) in necrotizing meningoencephalitis (NME) and interleukin-17 (IL-17) in granulomatous meningoencephalitis (GME) in tissue biopsies may indicate their potential as specific markers of NME and GME, respectively, suggesting further investigations of these in serum and CSF. While neuro-imaging is already an important part of the diagnostic work-up in MUO, further promising results have been shown with Positron Emission Tomography (PET) as well as proton resonance spectroscopy (¹H MRS), which may be able to detect areas of necrosis and granulomas, respectively, with relatively high specificity. This review presents different groups of established and potential diagnostic markers of MUO assessing current results and future potential.