The blood brain barrier (BBB) can be considered a friend and a foe. As its name implies the BBB is a living fortress that protects the brain from potentially harmful chemicals. While this is a very positive thing in our everyday lives, the BBB is a challenge when trying to get much needed therapies to brains that harbour cancers. In addition, cancers that metastasize from primary tumours and circulate in the blood stream have found ways to infiltrate the brain thereby hiding from therapies. These circulating cells have little understood special abilities to bind the cells of the BBB and enter the brain. We have developed a series of reproducible, dynamic in vitro ‘all human’ three dimensional (3D) models of the BBB for use in high throughput screening of potential therapeutics including nanoparticle-delivered treatment. In addition, we also use them to investigate mechanisms for breast and lung cancer cell attachment to the brain endothelium and subsequent infiltration across the BBB and colonization of the brain, resulting in significantly poorer prognoses.