This systematic review sought to assess the applications and implications of current medical informatics-based decision support systems related to medication prescribing and use. Studies published between January 2006 and July 2016 which were indexed in PubMed and written in English were reviewed, and 39 studies were ultimately included. Most of the studies looked at computerized provider order entry or clinical decision support systems. Most studies examined decision support systems as a means of reducing errors or risk, particularly associated with medication prescribing, whereas a few studies evaluated the impact medical informatics-based decision support systems have on workflow or operations efficiency. Most studies identified benefits associated with decision support systems, but some indicate there is room for improvement.