Abstract Purpose Health care requirements and perception of people with differences of sex development (DSD) have changed enormously since the “Chicago Consensus Conference” in 2005. Therefore, new standards of care and evaluation of care have to be developed. Methods We summarize the social and legal approach to care for DSD during the last two decades and report the main results of European research activities. Results The last two decades were accompanied by legal and societal discussion regarding how to deal with a nonbinary concept of sex. This leads to the necessity to assess health care requirements for individuals with DSD in an objective manner. We briefly review the results of the recently funded European research projects dealing with health-related issues in DSD like EU COST Action DSD, I-DSD, and dsd-LIFE, and address the compilation of quality indicators that will be needed to benchmark health care provision and health care-related outcomes. Conclusions The benchmarking process has to be implemented among health care providers for individuals with DSD within the European Reference Networks for Rare Conditions.