Zebrafish represent a vertebrate model organism that has been widely, and increasingly, employed over the last decade in the study of developmental processes, wound healing, microbe-host interactions, and drug screening. With the increase in the laboratory use of zebrafish, several advantages, such as a high genetic homology to humans and transparent embryos, which allow clear disease evaluation, have greatly widened its use as a model for studying tumor development in vivo. The use of zebrafish has been applied in several areas of cancer research, mainly in the following domains: (1) establishing cancer models by carcinogenic chemical, genetic technology, and xenotransplantation; (2) evaluating tumor angiogenesis; (3) studying tumor metastasis; and (4) anti-tumor drug screening and drug toxicity evaluation. In this study, we provide a comprehensive overview of the role of zebrafish in order to underline the advantages of using them as a model organism in cancer research. Several related successful events are also reviewed.