Drug addiction is a chronic relapsing disorder characterized by compulsive drug-seeking. There is lot of interest in gaining a better understanding of how acupuncture works in the brain to modulate addictive behaviors. The current study aims to discuss the neurobiological mechanisms underlying acupuncture’s effectiveness in the treatment of drug addiction, on the basis of two different theories (the incentive sensitization theory and the opponent process theory) that have seemingly opposite views on the role of the mesolimbic reward pathways in mediating compulsive drug-seeking behavior. Results provide evidence that acupuncture normalizes hyper-reactivity or hypoactivity of the mesolimbic dopamine system in these opposed processes in drug addiction by regulating neurotransmitters that control drug seeking. This proposes that acupuncture may reduce relapse to drug seeking by correcting both dysfunctions of the mesolimbic dopamine pathway via direct activation of brain pathways. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2018R1A5A2025272) (No. 2020R1A2C1006559).