In recent years, the healthcare sector has shown inclination towards restructuring of healthcare systems to harmonize with technological innovations and adopting decision support system in routine clinical practices. The objective of this paper is to summarize challenges of Clinical Decision Support System (CDSS) and focus on the effectiveness of CDSS to improve clinical practice. This paper also describes the experience of CDSS in healthcare sector in Saudi Arabia and addresses the requirements for implementing successful CDSS with a real example. This study concludes that healthcare sector is in dire need to increase quality of patients' care and improve clinical practices by adopting CDSS.