The genome can be studied with unprecedented depth and accuracy due to the dramatic increase in throughput of sequencing data from next-generation sequencing platforms. It has revolutionized the discovery of rare polymorphisms, structural variants, and novel transcripts. Our SureSelect Target Enrichment System for human exomes has proven to be an excellent tool for the accurate detection of common and rare SNPs, indels, CNVs, and splicing variants. Here we introduce exome kits for four model organisms, mouse, bovine, canine, and zebrafish. Each new exome kit demonstrates high performance as measured by specificity of capture, coverage depth, uniformity of coverage, and duplicate read counts. In addition to these four exomes kits, and to meet the demand for fast, cost-effective, and accurate genome analysis methods, Agilent’s eArray web-based software also supports the design of custom libraries for 16 unique species. We demonstrate that the SureSelect portfolio is a flexible system that is rapidly expanding to meet the needs of next-generation sequencing users. This creates a cost-effective approach to analyze specific genomic regions with unprecedented depth and accuracy. SureSelect Exome kits for mouse, bovine, canine, and zebrafish are a highly robust, customizable, and scalable system that enables next-generation sequencing users to focus their analysis on specific genomic loci at substantial cost-savings.