A long-term goal of pharmacogenomic research is the design of individualized therapy based on the genomic sequence of the patient in order to maximize response and minimize adverse drug reactions. Identifying genetic variants that predict drug response is challenging because drug responses reflect not only properties intrinsic to the target cell, but also host metabolic factors. One model that is currently being employed to study genotype-phenotype correlations involves the use of lymphoblastoid cell lines (LCLs). These cell lines have been used to identify genetic variation that influences response or susceptibility to cancer, radiation, transport, cytotoxicity, and variation in global gene expression. LCLs, particularly those derived from large pedigrees, are a valuable resource for identifying candidate genes and have potential for studies of many relevant phenotypes. This paper highlights studies that have utilized Centre d' Etude du Polymorphisme Humain (CEPH) and non-CEPH cell lines derived from humans for pharmacogenetic studies, and the advantages and disadvantages associated with this approach.