Delivering drugs to the brain is challenging given the selective permeability of the blood brain barrier (BBB). Targeted colloidal carriers containing drug payloads offer some promise for enhanced and perhaps selective delivery to brain. This review examines the recent literature and identifies issues to be addressed if these systems are to be rationally designed. These include opsonization of nanoparticles and off-target clearance; the cerebral microvasculature, flow of nanoparticles in capillaries and binding to the capillary wall; and transcytosis. Capillary architecture, blood flow and BBB permeability are affected by disease and age and there are species differences. These complexities caution against making extravagant claims for a particular nanosystem but they also highlight the rich opportunities and need for critical research in this field.