The rapid development of targeted therapies capable of entering the brain and the emerging technology of nano shells armed with cytotoxins reflects promising progress in the treatment of brain metastasis. The management of brain metastases is complicated by a number of major problems. The histological, molecular, biologic and immunologic nature of the various tumour types metastasizing to the brain differs significantly. As a consequence, the sensitivity towards various cytotoxic drugs or other treatment options varies substantially. Only few drugs are usually considered capable of penetrating the blood/brain and the brain/liquor barriers. Thus, the availability of a drug with adequate molecular size and pharmacokinetics within the compartments of the central nervous system determine the usage of cytotoxic drugs rather than the sensitivity of a specific tumour type to a specific drug. Recently, however, progress has been made in the development of more efficient types of therapy against brain metastases.