Posttraumatic stress disorder (PTSD) and substance use disorders (SUDs) co‐occur at high rates, with research showing that up to nearly 60% of individuals with PTSD also suffer from an alcohol and/or drug use disorder. PTSD/SUD is complex; associated with adverse health, social, and economic outcomes; and can be challenging to treat. Over the past decade, the landscape of treatment research addressing PTSD/SUD has significantly expanded. Ongoing efforts aimed at developing and evaluating novel treatments for PTSD/SUD, encompassing both psychotherapy and pharmacotherapy approaches, are steadily advancing. As such, this State of the Science paper reviews the literature on the latest scientific advances in treating PTSD/SUD. Clinical practice guidelines for the treatment of PTSD/SUD are discussed, along with evidence‐based psychotherapies and emerging interventions. Rigorously conducted clinical trials demonstrate that individual, manualized, trauma‐focused treatments are the most efficacious psychotherapies to use among individuals with PTSD/SUD. Moreover, patients do not need to be abstinent to initiate or benefit from evidence‐based PTSD treatment. To date, no medications have been established for this comorbidity. We highlight ongoing research on novel treatments for PTSD/SUD, such as new forms of integrated trauma‐focused psychotherapies, pharmacological augmentation strategies, and technology‐based enhancements. Finally, promising future directions for the field are discussed.