Oxymetazoline hydrochloride 0.05% is a lipophilic sympathomimetic nasal decongestant spray available over the counter (OTC) and commonly used for allergic and chronic rhinitis. A well-known side effect of these nasal sprays is rebound congestion termed rhinitis medicamentosa (RM), but there is little literature attesting to the relationship between RM and substance use disorder. This is a case report of severe nasal spray oxymetazoline use disorder per DSM-5 criteria discovered incidentally in a 44-year-old patient receiving care at a residential addiction treatment center for long-standing polysubstance use and bipolar disorders. The patient began using oxymetazoline in 2003 for allergic rhinitis and developed rhinitis medicamentosa that progressed to an oxymetazoline use disorder. Despite medical and clinical interventions, cravings and urges prevented her from stopping the nasal spray. We discuss the pharmacological properties of oxymetazoline, the behavioral aspects of its intranasal administration, and the drug-induced rebound congestion that may contribute to its misuse. To our knowledge, this is the first reported case of oxymetazoline use disorder lasting 20 years.