Clinical trials continue to fall short regarding drugs to effectively treat brain-affecting diseases. Althoughthere are many causes of these shortcomings, the most relevant are the inability of most therapeuticagents to cross the blood–brain barrier (BBB) and the failure to translate effects from animal models topatients. In this review, we analyze the most recent developments in BBB, neural, and neurovascularmodels, analyzing their impact on the drug development process by considering their quantitative andphenotypical characterization. We offer a perspective of the state-of-the-art of the models that couldrevolutionize the pharmaceutical industry.