Purpose of ReviewThis review reconsiders the role of precision lesioning as a potential therapeutic intervention for one of the most problematic types of addiction—substance use disorders (SUDs). Given the shared neurocircuitry and symptomatology between SUD and obsessive-compulsive disorder (OCD), and the established efficacy of lesioning in OCD, we examine the rationale for revisiting lesion-based approaches for addiction treatment.Recent FindingsModern lesioning techniques—including radiofrequency ablation (RFA), laser interstitial thermal therapy (LITT), stereotactic radiosurgery (SRS), and magnetic resonance-guided focused ultrasound (MRgFUS)—have significantly improved in precision and safety. While lesioning for addiction was explored from the 1950s to the early 2000s, it was largely abandoned due to ethical concerns and emerging alternatives like deep brain stimulation (DBS) and transcranial magnetic stimulation (TMS). However, recent neuroscientific advances have illuminated overlapping circuits in OCD and SUD, particularly involving the anterior cingulate cortex (ACC), anterior limb of the internal capsule (ALIC), dorsal striatum, and ventral striatum (nucleus accumbens). Lesioning the ACC or ALIC yields robust clinical improvements in OCD, and this may be translatable to addiction. Additionally, spontaneous addiction remissions following focal brain injury and emerging pre-clinical lesioning studies support this circuit-based approach.SummaryGiven the severity and treatment resistance of many SUD cases, precision-lesioning may offer a viable treatment option, as it has in OCD. With modern surgical technique, improved neuroimaging, and ethical oversight, targeted lesioning warrants renewed exploration through controlled trials. This approach may enable circuit-specific, personalized interventions for individuals who have exhausted guideline concordant therapy and face life-threatening consequences of ongoing addiction.