The zebrafish has emerged as a widely used model organism in drug discovery due to its fecundity, morphological and physiological similarity to mammals, and the availability of genomic tools. This article reviews the use of zebrafish in various stages of drug discovery, including target validation, disease modeling, lead discovery, and toxicology. The zebrafish's transparency, ease of genetic manipulation, and high-throughput phenotyping capabilities make it a valuable tool for these applications. Genetic and morpholino oligonucleotide screens have been used to identify novel drug targets, and whole-organism screens have been effective in identifying small molecules that suppress disease states. The zebrafish is also proving to be a useful model for toxicology, allowing for the assessment of compound safety earlier and more cost-effectively. Despite some limitations, the zebrafish offers a promising, low-cost, and efficient alternative to conventional animal models in drug discovery.The zebrafish has emerged as a widely used model organism in drug discovery due to its fecundity, morphological and physiological similarity to mammals, and the availability of genomic tools. This article reviews the use of zebrafish in various stages of drug discovery, including target validation, disease modeling, lead discovery, and toxicology. The zebrafish's transparency, ease of genetic manipulation, and high-throughput phenotyping capabilities make it a valuable tool for these applications. Genetic and morpholino oligonucleotide screens have been used to identify novel drug targets, and whole-organism screens have been effective in identifying small molecules that suppress disease states. The zebrafish is also proving to be a useful model for toxicology, allowing for the assessment of compound safety earlier and more cost-effectively. Despite some limitations, the zebrafish offers a promising, low-cost, and efficient alternative to conventional animal models in drug discovery.