Metastatic brain tumours are frequently observed in patients with lung, breast and malignant melanoma and a severe complication of metastatic cancers. With improved primary cancer treatments, including surgery, radiation therapy and chemotherapy, patients are now living longer following initial treatment, compared with previous treatments. Brain metastasis (BM) remains a significant clinical issue. Since BM represents a major therapeutic challenge, it is vital that the mechanisms of interaction between tumour cells and the blood-brain barrier (BBB), as well as the method by which tumour cells establish metastatic tumours in the brain, are understood. A key step in BM is the interaction and penetration of the BBB by cancer cells. The BBB consists of endothelial cells, pericytes, astrocytes and a number of molecular structures between these cells. The BBB relies on the tight junctions (TJs) that are present between the endothelial cells of the brain capillaries to provide a closed environment for the brain. TJs comprise a number of proteins, including occludin, claudins and junctional adhesion molecules (JAMs). Among them, claudins are the key integral proteins that regulate BBB permeability. It has previously been shown that claudin-5, not only regulates paracellular ionic selectivity, but also plays a role in the regulation of tumour cell motility, suggesting that TJs and claudin-5 contribute to the control of BM. This study reviews the role of claudin-5 in the regulation of BBB permeability during the brain metastatic process.