The blood-brain barrier (BBB) is a structural and functional barrier that protects the central nervous system (CNS) from invasion by blood-borne pathogens including parasites. However, some intracellular and extracellular parasites can traverse the BBB during the course of infection and cause neurological disturbances and/or damage which are at times fatal. The means by which parasites cross the BBB and how the immune system controls the parasites within the brain are still unclear. In this review we present the current understanding of the processes utilized by two human neuropathogenic parasites, Trypanosoma brucei spp and Toxoplasma gondii, to go across the BBB and consequences of CNS invasion. We also describe briefly other parasites that can invade the brain and how they interact with or circumvent the BBB. The roles played by parasite-derived and host-derived molecules during parasitic and white blood cell invasion of the brain are discussed.