Subspecies of the extracellular parasite, Trypanosoma brucei, which are spread by the tsetse fly in sub-Saharan Africa, cause in humans Sleeping Sickness. In experimental rodent models the parasite can at a certain stage of disease pass through the blood-brain barrier across or between the endothelial cells and the vessel basement membranes. The laminin composition of the basement membranes determines whether they are permissive to parasite penetration. One cytokine, interferon-gamma, plays an important role in regulating the trypanosome trafficking into the brain. Treatment strategies aim at developing drugs that can impede penetration of trypanosomes into the brain and/or that can eliminate trypanosomes once they are inside the brain parenchyma, but have lower toxicity than the ones presently in use.