Abstract: Since the early 2000s, the popularity of zebrafish in in vivo drug screening has shown a substantial increase. The zebrafish has become an important screening tool covering a wide range of tissue-specific pathologies and diseases/disorders. Nowadays phenotype-based screening is favoured over target-based screening approaches, because it can identify active drugs/small molecules in the absence of a known target or suspected mechanism of action. Phenotypic screens can identify not only compounds with a positive effect, but also compounds with off-target effect. Another advantage of whole-organisms screening is the bioavailability of compounds, and the fact that in vivo experiments will allow the normal metabolization of these compounds by the living organisms. Overall, this type of approach has boosted the discovery of higher quality compounds compared to in vitro target-based screens (Zhang and Peterson, 2019).