Human pluripotent stem cells (hPSCs), including embryonic stem cells isolated from the inner cell mass of a blastocyst (Thomson et al., 1998) and induced pluripotent stem cells (iPSCs) reprogrammed from somatic cells (Takahashi et al., 2007), could self-renew in vitro and have the potential to differentiate into any cell types of three germ layers. hPSCs and their derived cells could be used for genetic disease modeling, pathogenic mechanism investigation, and drug screening, and also provide unlimited cell resources for regenerative medicine. However, due to the differences between in vitro stem cell differentiation and in vivo development, most hPSCs-derived cells resemble fetal-stage cells and are not fully mature. Worldwide efforts are still on the way to generate functional tissue cells from stem cells. For this aim, we launched the specific Research Topic “Generation of Functional Tissues from Human Pluripotent Stem Cells” to highlight the latest progress to make functional cells from hPSCs and their applications. Throughout this Research Topic, we compiled various research papers from expert laboratories around the world within this exciting field of research.