First established as a valuable vertebrate model system for studying development, zebrafish have emerged as an attractive animal system for modeling human cancers. Major technical advances have been essential for the generation of zebrafish cancer models relevant to human diseases. These models develop tumors in various organ sites that bear striking resemblance to human malignances, both histologically and genetically. Thus, the focus of cancer research in zebrafish has transcended the need to validate zebrafish as a viable model organism to study cancer biology. With the significant advantages of in vivo imaging, the power of forward genetics, well-established high efficiency for transgenesis, and ease of transplantation, further exploration of the zebrafish cancer models not only will generate unique insights into underlying mechanisms of cancer but will also provide platforms useful for drug discovery.