The objective of the study was to identify potential barriers and facilitators to improve clinical practice using computer-based Clinical Decision Support System (CDSS). Studies published since 2000 were found using PubMed database, PsychInfo, CINAHL, EBSCOhost database, and Google scholar. Twenty-six relevant publications were examined. Thirty-five unique barriers and twenty-five unique facilitators were identified in the literature as important determinants of CDSS's adoption in clinical practice. The list of barriers and facilitators collected from each study were then organized under the four dimensions of The Unified Theory of Acceptance and Use of Technology (UTAUT) model: performance expectancy, effort expectancy, social influence, and facilitating conditions. Some of the important barriers to CDSS use include; lack of time or time constraints, economic constraints (e.g., finance and resources), lack of knowledge of system or content, reluctance to use system in front of patients, obscure workflow issues, less authenticity or reliability of information, lack of agreement with the system, and physician or user attitude toward the system. The study contributes immensely to the literature by identifying the important barriers and facilitators of CDSS.