In recent years in vivo chemical screening in zebrafish has emerged as a rapid and efficient method to identify lead compounds that modulate specific biological processes. By performing primary screening in vivo, the bioactivity, toxicity, and off-target side effects are determined from the onset of drug development. A recent study demonstrates that in vivo screening can be used successfully to perform structure-activity relationship (SAR) studies. This work validates the zebrafish as an effective model for not only drug discovery but also drug optimization.