This chapter presents several experimental approaches performed in the Laboratory of the Biology of Addictive Diseases to characterize the relationship of gene variations with heroin addiction and pharmacogenomics. Although opioid receptors often subserve similar physiological functions, activation of the kappa-opioid receptor (KOPr) by exogenous agonists produces dysphoria in humans and aversive effects in experimental animals, in contrast to activation of mu-opioid receptor (MOPr). Opiate addiction is a chronic relapsing disorder that is treated world-wide with methadone. The genes studied are usually those which have been shown to be involved in some aspects of development of addiction. In some studies, multiple genes, all hypothesized to be potentially involved in opioid addiction, have been studied. In other cases, genome-wide association studies (GWAS) have been performed to identify regions of chromosomes which may influence vulnerability to the development of addiction. These studies usually do not identify specific genes within chromosome regions.