The blood-brain barrier (BBB) hinders drug delivery to the brain parenchyma. The ultimate goal of brain drug targeting technology is to deliver therapeutics across the BBB with a diverse collection of molecular transport systems. Receptor-mediated transcytosis (RMT) is one such class of transport system. Insulin and transferrin, as well as other endogenous peptides, employ the vesicular trafficking machinery of the endothelium to transport substances between the blood and the brain. In addition to vector development, strategies for coupling drugs to the vector that give high-efficiency coupling are the other important element for RMT. After the BBB-targeting vector-therapeutic conjugates have crossed the BBB, there may still be a need to target them to a specific population of cells in the brain. This review will focus on two major aspects of RMT brain drug delivery: new advances of existing RMT systems and development of new BBB transport vectors and specific RMT targets.