Purpose of Review <p>Brain disorders such as Alzheimer’s disease, Parkinson’s disease, glioblastoma, and epilepsy remain difficult to treat due to the restrictive blood–brain barrier (BBB). In vitro to in vivo extrapolation (IVIVE) has emerged as a translational framework to connect preclinical findings with clinical relevance, particularly for brain-targeted drug development.</p> Recent Findings <p>Current IVIVE methodologies integrate data from diverse in vitro BBB models, including static transwells, co-cultures, microfluidic chips, and 3D organoids, with computational approaches such as physiologically based pharmacokinetic (PBPK) modeling and hybrid strategies. Case studies illustrate successful applications of IVIVE to both small molecules and biologic therapeutics, while also highlighting limitations such as variability in barrier models, incomplete transporter representation, and translational uncertainty.</p> Summary <p>Future advances in BBB models, high-throughput screening, and AI-enhanced modeling promise to improve predictive accuracy. IVIVE holds strong potential to accelerate safe, effective, and precision-targeted therapies for brain diseases.</p>