Background: Currently many healthcare systems are supported by an increasing set of Health Information Sys-tems (HISs), which assist the activities for multiple stakeholders. The literature on HISs is, however, fragmented and a solid overview of the current state of HISs is missing. This impedes the understanding and characterization of the required HISs for the healthcare domain. Methods: In this article, we present the results of a Systematic Literature Review (SLR) that identifies the HISs, their domains, stakeholders, features, and obstacles. Results: In the SLR, we identified 1340 papers from which we selected 136 studies, on which we performed a full-text analysis. After the synthesis of the data, we were able to report on 33 different domains, 41 stakeholders, 73 features, and 69 obstacles. We discussed how these domains, features, and obstacles interact with each other and presented suggestions to overcome the identified obstacles. We recognized five groups of obstacles: technical problems, operational functionality, maintenance & support, usage problems, and quality problems. Obstacles from all groups require to be solved to pave the way for further research and application of HISs. Conclusion: This study shows that there is a plentitude of HISs with unique features and that there is no consensus on the requirements and types of HISs in the literature.