Recent advancements in neuroimaging and genetic techniques have significantly transformed our understanding of the neurobiological mechanisms underlying substance use disorders (SUDs). Optogenetic and chemogenetic approaches, in conjunction with traditional neuroimaging methods, have offered unprecedented insights into the brain’s response to psychoactive substances. This chapter reviews the current state of knowledge concerning these techniques and their applications in addiction research, highlighting their contributions to elucidating drug-seeking behaviors, neural circuitry, and potential therapeutic strategies.