Behavioral health organizations have been increasingly required to implement plans to monitor and improve service quality. This qualitative study explores challenges that quality assurance and improvement (QA/I) personnel experience in performing their job in those practice settings. Sixteen QA/I personnel from different agencies in St. Louis, Missouri, U.S.A., were interviewed face-to-face using a semi-structured instrument to capture challenges and a questionnaire to capture participant and agency characteristics. Data analysis followed a grounded theory approach. Challenges involved agency resources, agency buy-in, personnel training, competing demands, shifting standards, authority, and research capacity. Further research is needed to assess these challenges given expected outcomes.