Organs-on-a-Chip (OoC), micro-engineered cell culture models, have emerged as a new tool to recapitulate human physiology and drug responses. Several studies have shown that Organs-on-a-Chips can accurately recapitulate the multicellular architectures, vascular-parenchymal tissue interfaces, chemical gradients, mechanical cues, and vascular perfusion of the body. It is possible to mimic human disease states, as well as the functionality of tissues and organs, in a way that conventional 2D or 3D culture systems cannot. In our lab, we develop OoC as predictive human models of the Central Nervous System so that therapies for neurodegenerative diseases can be investigated, overcoming current models’ limitations and reducing animal testing.