The authors describe the use of zinc finger nucleases (ZFNs) to achieve somatic and germline gene disruption in zebrafish, a model organism with limited reverse genetic tools. ZFNs induce double-strand breaks in the genome, which are repaired to generate small insertions and deletions. They designed ZFNs targeting the *golden* (*gol*) and *no tail/Brachyury* (*ntl*) genes. Injection of ZFN-encoding mRNA into 1-cell embryos resulted in a high percentage of animals carrying distinct mutations at the specified positions, exhibiting expected loss-of-function phenotypes. Disrupted *ntl* alleles were transmitted from ZFN mRNA-injected founder animals in over half of the adults tested, with an average frequency of 20%. The study demonstrates the feasibility and precision of using ZFN technology for gene disruption in zebrafish, opening new avenues for experimental research and suggesting its potential application in other organisms.The authors describe the use of zinc finger nucleases (ZFNs) to achieve somatic and germline gene disruption in zebrafish, a model organism with limited reverse genetic tools. ZFNs induce double-strand breaks in the genome, which are repaired to generate small insertions and deletions. They designed ZFNs targeting the *golden* (*gol*) and *no tail/Brachyury* (*ntl*) genes. Injection of ZFN-encoding mRNA into 1-cell embryos resulted in a high percentage of animals carrying distinct mutations at the specified positions, exhibiting expected loss-of-function phenotypes. Disrupted *ntl* alleles were transmitted from ZFN mRNA-injected founder animals in over half of the adults tested, with an average frequency of 20%. The study demonstrates the feasibility and precision of using ZFN technology for gene disruption in zebrafish, opening new avenues for experimental research and suggesting its potential application in other organisms.