Isocitrate dehydrogenase (IDH) mutations are a common event in secondary glioblastoma multiforme and lower-grade adult infiltrative astrocytomas and independently confer a better prognosis [1,2]. These are highly conserved mutations during glioma progression and thus also a useful diagnostic marker amenable to modern molecular sequencing methods. These mutations can even be detected in sites distant from the primary tumour. We use an illustrative case of a patient with radiologically suspected recurrent astrocytoma and negative histology, but positive IDH-mutated tumour DNA detected within CSF. Our results demonstrated the usefulness of liquid biopsy for recurrent glioma within the context of equivocal or negative histopathological results, whilst also showing the ability to detect a de-novo IDH-2 mutation not present in the previous resection. Building on this ‘proof-of-concept’ result, we also take the opportunity to briefly review the current literature describing the various liquid biopsy substrates available to diagnose infiltrative gliomas, namely the study of circulating tumour DNA, circulating tumour cells, and extracellular vesicles. We outline the current challenges and prospects of liquid biopsies in these tumours and suggest that more studies are required to overcome these challenges and harness the potential benefits of liquid biopsies in guiding our management of gliomas.