Over the past 15 years, zebrafish have emerged as a powerful tool for studying human cancers. Transgenic techniques have been employed to model different types of tumors, including leukemia, melanoma, glioblastoma and endocrine tumors. These models present histopathological and molecular conservation with their human cancer counterparts and have been fundamental for understanding mechanisms of tumor initiation and progression. Moreover, xenotransplantation of human cancer cells in embryos or adult zebrafish offers the advantage of studying the behavior of human cancer cells in a live organism. Chemical-genetic screens using zebrafish embryos have uncovered novel druggable pathways and new therapeutic strategies, some of which are now tested in clinical trials. In this review, we will report on recent advances in using zebrafish as a model in cancer studies-with specific focus on four cancer types-where zebrafish has contributed to novel discoveries or approaches to novel therapies.