This commentary discusses the need for developing patient registries of substance use disorders (SUD) in general medical settings. A patient registry is a tool that documents the natural history of target diseases. Clinicians and researchers use registries to monitor patient comorbidities, care procedures and processes, and treatment effectiveness for the purpose of improving care quality. Enactments of the Affordable Care Act 2010 and the Mental Health Parity and Addiction Equity Act 2008 open opportunities for many substance users to receive treatment services in general medical settings. An increased number of patients with a wide spectrum of SUD will initially receive services with a chronic disease management approach in primary care. The establishment of computer-based SUD patient registries can be assisted by wide adoption of electronic health record systems. The linkage of SUD patient registries with electronic health record systems can facilitate the advancement of SUD treatment research efforts and improve patient care.