The toxicological risk of Co-Cr dental alloys is actually a sensitive subject with the European regulatory changes, namely regulation (EU) 2017/745 and annex VI to the CLP regulation (EC) 1972/2008. : The objective of this review is to conduct a rigorous analysis of the cytocompatibility of cobalt-chromium (Co-Cr) dental alloys. Considering various parameters such as cytotoxicity, type IV hypersensitivity reaction, sensitization, and irritation, we investigated evidence of toxicity of Co-Cr in human dental applications. : Specific search strategies were performed in three electronic databases, namely Medline, Embase, and Web of Science, using a main restriction in the search regarding the publication date (1995-2022). : Out of a total of 836 articles, only 21 studies were selected and analyzed according to PRISMA methodology. : Among them, 10 in vitro studies using human samples and 11 in vivo studies on human patients were distinguished. Most of the in vitro studies confirmed that Co-Cr alloys have a good cytocompatibility compared to Ni alloys. Regarding the in vivo studies, it appeared that Co-Cr could rarely cause sensitization, irritation, and allergic reactions. Reactions were mainly observed for people allergic to Co or Cr. Nevertheless, titanium-based materials showed better results. : This study proposes a new state of the art on Co-Cr dental alloys and will thus be very useful for carrying out additional studies. : This review will help practitioners in their daily clinical choice.