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In this article, we describe contrasting developmental aspects of paediatric and adult brain tumours. We hypothesize that the formation of cancer progenitor cells, for both paediatric and adult, could be due to epigenetic events. However, the progression of adult brain tumours selectively involves more mutations compared to paediatric tumours. We further discuss epigenetic switches, comprising both histone modifications and DNA methylation, and how they can differentially regulate transcription and expression of oncogenes and tumour suppressor genes. Next, we summarize the currently available therapies for both types of brain tumours, explaining the merits and failures leading to drug resistance. We analyse different mechanisms of drug resistance and the role of epigenetics in this process. We then provide a rationale for combination therapy, which includes epigenetic drugs. In the end, we postulate a concept which describes how a combination therapy could be initiated. The timing, doses, and order of individual drug regimens will depend on the individual case. This type of combination therapy will be part of a personalized medicine which will differ from patient to patient.