Zebrafish are a popular model organism for studying embryonic vascular development. Recent studies have shown that clinical stage anti-angiogenic compounds can inhibit vascular growth in zebrafish. In this issue, Tran and colleagues sought to use zebrafish as a tool to discover new anti-angiogenic compounds. Transgenic zebrafish expressing a green fluorescent reporter protein specifically in the vasculature were employed to develop an automated, quantitative screening assay for anti-angiogenic compound activity. The methods developed include automated determination of angiogenic blood vessel count in the trunk of zebrafish embryos. The assay was used to screen a 1280 compound library. Two known anti-angiogenic compounds were identified in the screen. Additionally, a novel anti-angiogenic compound, indirubin-3’-monoxime, was discovered. These results show that zebrafish can be used as a drug discovery tool to identify newanti-angiogenic compounds. For details, see the article by Tran and colleagues on page 11386 of this issue.