Abstract: Rare diseases are a general term for a large number of special diseases. They are characterized by early onset, seriously phenotype, and poor prognosis, bringing a huge burden to families and society. The vast majority of rare diseases are genetic diseases. Precision medicine, which is based on individual genomes, has been proven an effective means to study rare diseases and has made continuous breakthroughs in genetic mechanisms, clinical classification and treatment development. Despite the great achievements made in precision medicine for rare diseases, we should also see the problems: more than 40% of diseases have not yet found any pathogenic gene； the genotypes and clinical phenotypes are not clear in many rare disease； more than 90% of rare diseases lack targeted drugs. In response to the national policy of "life first", we discuss the challenges of precision medicine for rare diseases in a series of actions to be taken in order to strengthen basic research on rare diseases, to accelerate the research and development of rare disease drugs, and to bring more warmth and hope to patients with rare disease and their families.