Historically, zebrafish (Danio rerio) have been a powerful model organism to interrogate vertebrate development via systematic mutational and forward genetic approaches. Zebrafish have also become popular recently as an experimental system for studying human pathology, including many cancers. In the past few years, several transgenic zebrafish models have been engineered that develop hematologic malignancies, corresponding to both lymphoid and myeloid neoplasias. These transgenic lines have utilized previously known mammalian proto-oncogenes or human translocation-derived fusion proteins to initiate malignant transformation. In aggregate, these models show striking similarities to human cancers. As such, they represent useful tools for dissecting the molecular details of the pathogenic mechanisms operative in these specific diseases. Zebrafish are also amenable to large-scale phenotypic mutagenesis screens, and thus are potentially useful for detecting unknown oncogenic mutations as well. We have recently employed this experimental strategy to isolate several mutants with heritable predisposition to T cell lymphocytic cancers. Here, we review zebrafish models of human hematologic malignancy generated to date, how these systems have been exploited in the past, and the future avenues they offer to improve our understanding of leukemo- and lymphomagenesis.