Clinical Decision Support Systems have been shown to increase quality of care, patient safety, improve adherence to guidelines for prevention and treatment, and avoid medication errors. Such systems depend mainly on two types of content; the clinical information related to patients and the medical knowledge related to the specialty that informs the system rules and alerts. At King Faisal Specialist Hospital and Research Center, Saudi Arabia, the Health Information Technology Affairs worked on identifying best strategies and recommendations for successful CDSS knowledge management. A review of literature was conducted to identify main areas of challenges and factors of success. A qualitative survey was used over six months' duration to collect opinions, experiences and suggestions from both IT and healthcare professionals. Recommendations were categorized into ten main topics that should be addressed during the development and implementation of CDSS knowledge management tools in the hospital.