Inflammation in the central nervous system (CNS) contributes to disease pathologies by disrupting the integrity of the blood–brain barrier (BBB). Tight junctions (TJ) are a key component of the BBB. Following hypoxic–ischaemic or mechanical injury to the brain, inflammatory mediators are released such as cytokines, chemokines, and growth factors. Simultaneously, matrix metalloproteinases (MMPs) are released which can degrade TJ proteins. Subsequently, the function and morphology of the BBB are disrupted, which allows immune cells an opportunity to enter into the brain parenchyma. This review summarises the information on the role of TJ protein families in the BBB and provides a comprehensive summary of the mechanisms whereby inflammation breaks down the BBB by increasing degradation of TJ proteins.