Zebrafish is a powerful system for studies of embryogenesis and to investigate mechanisms underlying human diseases. The zebrafish is particularly well suited to study complex and acquired diseases and to identify new disease genes owing to its genetic tractability, transparency of the organism, and the ease of conducting chemical screens to identify diagnostic and potential therapeutic targets. Moreover, the high degree of genetic conservation renders translation between fish and mammals a possibility. For example, this model system can be used to validate and characterize genome-wide association study (GWAS) candidates through gain of function and loss of function approaches. For loss of function analysis the candidate, the gene of interest can be transiently knocked down or stable mutant alleles can be generated through reverse genetic mutagenesis approaches. The phenotypes produced by the normal and mutant versions can provide an indication of the gene’s function in development and disease. The Einstein Zebrafish Core was established to facilitate this type of analysis.