As is the case for many human disorders, cardiovascular disease is a complex ailment exhibiting a multifactorial mode of transmission. Rat models have been developed to aid in the analysis of this complex genetic and phenotypic disorder. The purpose of this brief review is to describe current gene expression profiling strategies that have been implemented to search for candidate causative genes of disease phenotypes in animal models. Strategies include integrating gene expression information with linkage analysis, expression profiling chromosome-substituted and/or congenic rat strains, correlating gene expression with physiological data across a panel of rodent strains, and linking expression quantitative trait loci to physiological quantitative trait loci. A primary goal of these strategies is to narrow and prioritize the search for causal genes of physiological interest. Also discussed are ways to harness two recent publicly available resources that have been created to investigate the role of genes and environment on cardiovascular physiology and pathophysiology.