For historical, social, political and religious reasons, Italy has traditionally approached life sciences, especially those involving humans, with great caution. The main law touching on human germline genome modification, called Law 40/2004 (‘Rules on Medically Assisted Reproduction’) bans most ‘experimentation’ on human embryos. In addition, EU Regulation 536/2014 contains a ban on clinical research using germline modification technologies. Nevertheless, Article 13 of Law 40/2004 leaves the door open to clinical applications of germline modification technologies. However, only the improvement of basic research on gametes would permit in the future to decide if, and possibly identify which, clinical applications are scientifically feasible and ethically acceptable. Recent developments and new possibilities in the field of human germline genome modification call for regulations that, while setting limits to contain possible abuses, do not wholly frustrate scientific and technological progress. Moreover, human germline genome modification technologies, which have enormous therapeutic potential, can further certain values enjoying a constitutional status under the Italian legal system, such as the promotion of scientific progress and the protection of health.