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Most cancer therapeutics that show preclinical promise fail in clinical trials, underscoring the need for complementary disease models. Over the past two decades, zebrafish models have matured from a tool for studying vertebrate development into a versatile platform spanning the translational cancer pipeline. Transgenic and transplantation zebrafish models have dissected fundamental mechanisms of tumor initiation and metastasis. Beyond mechanistic insight, phenotypic chemical and genetic screens provide a rapid, whole-organism filter to prioritize and repurpose therapeutic candidates, several of which have reached the clinic. Most recently, zebrafish patient-derived xenografts have begun to predict individual patient treatment responses within clinically actionable timeframes. Tracing this evolution, we argue that zebrafish models are not a replacement for other systems but earn their translational value when applied to the questions they answer best and when embedded in co-clinical workflows alongside oncology teams.