SummaryObjective: The year 2020 was predominated by the coronavirus disease 2019 (COVID-19) pandemic. The objective of this article is to review the areas in which clinical information systems (CIS) can be and have been utilized to support and enhance the response of healthcare systems to pandemics, focusing on COVID-19.Methods: PubMed/MEDLINE, Google Scholar, the tables of contents of major informatics journals, and the bibliographies of articles were searched for studies pertaining to CIS, pandemics, and COVID-19 through October 2020. The most informative and detailed studies were highlighted, while many others were referenced.Results: CIS were heavily relied upon by health systems and governmental agencies worldwide in response to COVID-19. Technology-based screening tools were developed to assist rapid case identification and appropriate triaging. Clinical care was supported by utilizing the electronic health record (EHR) to onboard frontline providers to new protocols, offer clinical decision support, and improve systems for diagnostic testing. Telehealth became the most rapidly adopted medical trend in recent history and an essential strategy for allowing safe and effective access to medical care. Artificial intelligence and machine learning algorithms were developed to enhance screening, diagnostic imaging, and predictive analytics - though evidence of improved outcomes remains limited. Geographic information systems and big data enabled real-time dashboards vital for epidemic monitoring, hospital preparedness strategies, and health policy decision making. Digital contact tracing systems were implemented to assist a labor-intensive task with the aim of curbing transmission. Large scale data sharing, effective health information exchange, and interoperability of EHRs remain challenges for the informatics community with immense clinical and academic potential. CIS must be used in combination with engaged stakeholders and operational change management in order to meaningfully improve patient outcomes.Conclusion: Managing a pandemic requires widespread, timely, and effective distribution of reliable information. In the past year, CIS and informaticists made prominent and influential contributions in the global response to the COVID-19 pandemic.