The development of brain metastases is still considered as a "terminal complication" of a cancer disease. The potential for CNS metastases appears to be greatest in tumours of neuroectodermal origin like melanoma or SCLC, very high in patients with tumours of ectodermal origin like breast cancer and NSCLC, whereas tumours arising from other embryonic origin develop brain metastases less often. Neovacularisation with upregulated VEGF Expression by the tumour cells facilitates their transmigration through the BBB. Temozolomide and "small molecules" are currently under investigation in solid tumours as farnesyltransferase inhibitors and tyrosin kinase inhibitors are able to cross BBB and thus should be active within the brain. Although studies on chemotherapy of brain metastases are usually small and include mostly a small number of patients, responses and prolongations of survival have been recorded. More studies are needed to evaluate the potential of the new therapeutics agents which increased therapeutic ratio and reduced side effects from chemotherapy.