Breakthroughs in stem cell biology and microfluidics technology have opened doors to in vitroscreening platforms for personalized testing of safety (pharmaceuticals, nutrients, chemicals) and efficacy (pharmaceuticals, nutraceuticals). Major breakthrough technologies include development of induced pluripotent stem cells, the development of induced pluripotent stem cell-derived organoids and adult stem cell-derived organoids, and the generation of organ-on-a-chip and multi-organ-on-a-chip models to mimic human physiology in vitro. These technologies are highly complementary and offer tremendous potential for improved efficiency in drug development and chemical safety testing. In the current review, we will provide an overview of recent advances in in vitromodeling for personalized drug testing based on stem cell and organ-on-a-chip technologies and illustrate how these developments will eventually lead to the replacement of animal testing. Particular focus will be on multi-organ-on-chip human disease models, which have the potential to be the gold standard of the future for the investigation of safety, toxicity, and efficacy of newly developed medicines.