Brain diseases such as Alzheimer’s, Parkinson’s, multiple sclerosis (MS), and brain tumors are difficult to diagnose and treat. This is partly due to the difficulty in delivering diagnostic and therapeutic molecules across the blood–brain barrier (BBB) and into the brain. This chapter describes challenges and the progress that have been made in transporting molecules into the brain. The pathways that molecules can take to cross the BBB and methods to improve the passage of diagnostics and therapeutic molecules into the brain are described. Several advances in improving detection of molecules in the brain using imaging methods (i.e., MRI, PET, SPECT, NIR) are described as potential diagnostic tools for brain diseases.