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The zebrafish (Danio rerio) is a useful animal model system for studying genetics, cardiovascular development, and cardiotoxicity. Recently, extensive chemical and drug toxicity screening have been conducted using zebrafish embryos. Relevance and predictability of drug response between zebrafish and humans have been studied, and it has been found that zebrafish show a high percentage of predictability (78% and 70%) of drug response. Both the mammalian and zebrafish heart share the development of specialized chambers, valves to ensure directionality, outflow tracts to an intricate vasculature, specialized endothelial cells to drive a high-pressure system, and an electrical system to regulate the rhythm. Besides, cardiac performance in adult zebrafish can be detected by new noninvasive methods. It can be assessed by advancing conventional echocardiography with speckle-tracking analyses and changes in cardiac performance, and allows highly sensitive assessment of regional myocardial motion and deformation in high spatio-temporal resolution.