The brain has long been recognised as a site with a very low rate of metastases, despite the potential for cancers to be extremely locally aggressive. This feature contrasts with most of the rest of the body, where metastatic spread is much more common. The pathological behaviour of any tumour is governed by both its inherent composition and the composition of the matrix in which it is sited. Much work has been done in recent years to elucidate the factors within the central nervous system (CNS) that give the brain its unique properties. Tumour interactions with the blood–brain barrier, microglia, and various matrix proteins, cytokines, and growth factors have a central role. This review concentrates mainly on the process of tumour spread from the CNS and explores how the brain is a protected site. CNS metastases from extraneural sites are also briefly covered.