The blood brain barrier (BBB) plays an important role in the homeostatic regulation of the brain microenvironment and maintains the immune-privileged status of the brain by restricting the entry of T lymphocytes. Structurally, the BBB is formed by tight junctions between the endothelial cells. Astrocytes, pericytes and perivascular microglia surround the endothelial cells contributing to proper functioning of the BBB. Hypoxia, associated with disorders such as stroke, cardiac arrest, respiratory distress, carbon monoxide poisoning among many others, disrupts the BBB. Alterations in the endothelial cells such as increased pinocytotic vesicles and derangement of the tight junction proteins may be responsible for increased permeability at the BBB resulting in swelling of astrocyte end feet. The disruption of BBB in hypoxic conditions is multifactorial and may involve factors such as enhanced production of vascular endothelial growth factor (VEGF), nitric oxide (NO) and inflammatory cytokines. Although future research is needed to look into possible therapeutic strategies to improve the functioning of BBB in hypoxic conditions, experimental studies so far have reported beneficial effect of curcumin, melatonin, simvastatin and minocycline in ameliorating the increased BBB permeability in hypoxic conditions.