The devastating disease of human cancers is a global health concern. In the past, development of effective therapies has been hindered by a shortage of reliable models; but in recent years, experimental models of human cancer for research are becoming more sophisticated. In this special issue consisting of series of seven short reviews, investigators working on different cancer types and experimental models summarize updated knowledge and present perspectives on some of the recent progress in human cancer modeling. Specifically, modeling leukemia, breast, ovarian and liver cancers by zebrafish, mouse and organoids are reviewed, with their strengths and limitations highlighted.