Temozolomide is an oral chemotherapy used to treat aggressive pituitary tumours since 2006. It is inexpensive and well tolerated, the main side effects are fatigue, nausea and cytopenia. Overall the studies demonstrate approximately 70% response rate for temozolomide, if response is defined radiologically as complete, partial response or stable disease. Using the more stringent criteria of complete or partial response, the success rate is near 40%. Functioning tumours respond more frequently than non-functioning tumours. Tumours which are depleted of methyl guanine methyltransferase (MGMT), as assessed by immunohistochemistry, also are more likely to respond. Temozolomide has an established role in treating pituitary tumours which have demonstrated metastases or which are refractory and progressing, despite all conventional treatment (so-called salvage treatment). The challenge is to offer temozolomide earlier in the pathway if appropriate. Tumours which demonstrate aggressive clinical behaviour (defined as clinically relevant growth despite optimal treatment) should be considered for temozolomide. One common situation when this might occur is tumour progression after surgery and radiotherapy. It is unnecessary to wait until salvage treatment is required. Anticipated (but not yet demonstrated) aggressive behaviour can be regarded as a potential indication for temozolomide, but there is currently insufficient evidence to recommend this. Ideally a trial should assess this potential indication. Early treatment could be considered in selected cases when high levels of proliferation and invasion were demonstrated, causing significant clinical concern.