Chronic pruritus is one dermatologic manifestation of an underlying substance use disorder. Recent literature has uncovered similarities between the general neurologic mechanisms of addiction and chronic itch, largely involving activation of the dopaminergic reward circuits within the brain and imbalances between mu and kappa opioid receptor activation. It is likely that the use of specific drugs, like central nervous system stimulants and opioids, results in further activation and imbalances within these pathways, perpetuating both addiction and pruritus simultaneously. Opioid users often present to dermatology clinics with a generalized pruritus, whereas individuals using central nervous system stimulants like cocaine and methylenedioxymethamphetamine (MDMA), as well as legally prescribed drugs like treatments for attention deficit hyperactivity disorder, frequently complain of crawling, delusional infestation–like sensations underneath the skin. Because of these overlapping mechanisms and similar clinical presentations to many other chronically itchy conditions, it is necessary for dermatologists to consider and investigate an underlying substance use disorder to effectively treat these patients.