I will discuss our work on the development of human Organ-on-a-Chip (Organ Chip) microfluidic culture devices lined by living human cells to replace animal testing, accelerate drug development, discover new biomarkers, and advance personalized medicine. Our Organ Chips are effectively living 3D cross sections of major functional units of living organs that contain human organ-specific epithelial cells interfaced with human microvascular endothelial cells that are exposed to fluid flow to mimic vascular perfusion. We also recreate the relevant physicochemical microenvironment of each organ, for example, by recreating breathing motions and an air-liquid interface in lung and trickling flow and peristalsis-like deformations in intestine. We have engineered multiple human Organ Chips, including lung (alveolus and airway), intestine (duodenum, ileum, colon), kidney (proximal tubule and glomerulus), bone marrow, liver, and blood-brain barrier (BBB) chips, as well as fluidically linked BBB Chips and brain neuronal network chips. This Organ Chips have been used to develop various human disease models and uncover new drug targets and potential clinical biomarkers, as well as discover new therapeutics. In addition, multiple different human Organ Chips have been fluidically linked to create an automated 'human Body-on-Chips' for real-time analysis of cellular responses to pharmaceuticals, chemicals, and toxins, as well as for quantitative in vitro-to-in vivo translation (IVIVT) of human drug pharmacokinetics in vitro.