The vital goal of most biomedical research is to understand the cellular and molecular mechanisms of human disease or to develop novel and innovative therapies or diagnostics. Although animal models, such as transgenic mice, provides crucial clues of many diseases, many of them fail to recapitulate the human disease condition precisely. Furthermore, it is hard to recognize crucial cellular and molecular contributors to disease or gain greater insights in whole-animal models. Recent advances in tissue engineering and microfabrication technologies have generated huge interest in researchers to develop novel in vitro disease models to solve this problem. Among various microfabrication techniques, 3D printing is one such technique that enables researchers to build 3D in vitro tissue models, where the intrinsic cellular morphologies and functions can be reconstituted. These models allow the researchers to vary the specific cellular and molecular factors independently while simultaneously measuring system-level responses in real time. In this chapter, we provide some proof of concept examples of such efforts for engineering disease models. We also discuss the recently developed tools and technologies in 3D printing to develop these models and emphasize opportunities and challenges involved in combining these technologies. © 2017 Elsevier Ltd. All rights reserved.