Background The patient monitor (PM) is one of the most commonly used medical devices in hospitals worldwide. PMs are used to monitor patients’ vital signs in a wide variety of patient care settings, especially in critical care settings, such as intensive care units. An interesting observation is that the design of PMs has not significantly changed over the past 2 decades, with the layout and structure of PMs more or less unchanged, with incremental changes in design being made rather than transformational changes. Thus, we believe it well-timed to review the design of novel PM interfaces, with particular reference to usability and human factors. Objective This paper aims to review innovations in PM design proposed by researchers and explore how clinicians responded to these design changes. Methods A literature search of relevant databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, identified 16 related studies. A detailed description of the interface design and an analysis of each novel PM were carried out, including a detailed analysis of the structure of the different user interfaces, to inform future PM design. The test methodologies used to evaluate the different designs are also presented. Results Most of the studies included in this review identified some level of improvement in the clinician’s performance when using a novel display in comparison with the traditional PM. For instance, from the 16 reviewed studies, 12 studies identified an improvement in the detection and response times, and 10 studies identified an improvement in the accuracy or treatment efficiency. This indicates that novel displays have the potential to improve the clinical performance of nurses and doctors. However, the outcomes of some of these studies are weakened because of methodological deficiencies. These deficiencies are discussed in detail in this study. Conclusions More careful study design is warranted to investigate the user experience and usability of future novel PMs for real time vital sign monitoring, to establish whether or not they could be used successfully in critical care. A series of recommendations on how future novel PM designs and evaluations can be enhanced are provided.