To identify major genes influencing the complex disease process of atherosclerosis, the strategy for collection of study materials should be designed with care to enrich the genetic factors. The tools for an efficient gene search are provided by the Human Genome Program; current genetic maps with dense marker sets provide a basis for genome-wide scans, and close to complete physical maps and identification of coding regions of all human genes within next few years offer the scaffolding for the final recognition of genes predisposing to atherosclerosis. The statistical methods applicable in the initial gene search of complex diseases have developed during recent years including now exact modifications of association analysis, also advanced multipoint analyses applicable in both parametric (linkage analysis) and nonparametric (affected sib-pair) methods and maximizing the information extractable from individual genotypes. Genome scans in the relevant animal models will often guide to important genomic regions, and genetically modified animals will be of essential importance for final understanding of the molecular pathogenesis of atherosclerosis.