The blood-brain barrier (BBB) is a dynamic and complex interface between the blood and the central nervous system regulating brain homeostasis. Major functions of the BBB include the transport of nutrients and protection of the brain from toxic compounds. This review summarizes the most important transport pathways contributing to the nutrition of the brain. Carrier-mediated transport selectively delivers small molecules like sugars, amino acids, vitamins, and trace elements. Large biomolecules, lipoproteins, peptide and protein hormones cross the BBB by receptor-mediated transport. Active efflux transporters participate in the brain efflux of endogenous metabolites as well as toxins, xenobiotics and drugs. Dysfunction in the transport of nutrients at the BBB is described in several neurological disorders and diseases. The BBB penetration of neuroprotective nutrients, especially plant polyphenols and alkaloids, their potential protective effect on brain endothelium and the interaction of nutraceuticals with active efflux transporters at the BBB are discussed. In vitro BBB models to examine nutrient transport are also presented. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.