There are more than 7,000 rare genetic diseases in Canada, which have a devastating impact on some one million Canadians and their families: two-thirds of these diseases cause significant disability; threequarters affect children; more than half lead to early death; and, almost none has any targeted treatment. Further, more than one-third of these diseases remain unsolved (their genetic cause is unknown). Building on the work of the Care4Rare Canada Consortium, the C4R-SOLVE project is working to identify the genetic cause of unsolved rare diseases and make genomic sequencing available to Canadians for rare disease diagnosis. Genomic sequencing will speed up the diagnostic process, thereby ending or even preventing years of diagnostic testing and visits to multiple specialists. Providing a timely diagnosis improves the care and wellbeing of patients and their families and reduces unnecessary healthcare spending. Key to C4R-SOLVE’s success will be new sequencing technologies and improved worldwide data sharing. In addition, the group will work with provincial ministries of health to determine how best to include genomic sequencing as a clinical test to diagnose rare diseases, beginning with Alberta and Ontario. In doing so, C4R-SOLVE will more than double our ability to diagnose unsolved rare disease, while building the infrastructure and tools needed to improve rare disease diagnosis worldwide. Accurate and early diagnosis will optimize care, improve the wellbeing of patients and their families, provide new insights into these devastating diseases, and potentially save at least $28 million/year in health-care spending.