Treatment-refractory or treatment failure cases can be quite challenging for a clinician. Utilizing a multi-disciplinary approach with a comprehensive view of a difficult case may be a helpful strategy to assess the diagnosis and come up with strategies to move treatment forward. This CCC focuses on these challenging cases to better understand the multitude of factors that may interfere with treatment and identify areas for making improvement, such as psychopharmacology, family dynamics, psychodynamics, cognitive distortions, cultural factors, and others. Presenters share cases where standard treatment proved to be inadequate in addressing the particular child, adolescent, or family’s needs and look at comprehensive, multi-disciplinary approaches that may offer new insights into approaching these cases.