Genomic information has the potential to improve management or potentially prevent or enable early intervention of virtually every disease. However, despite massive technological leaps and exponential decreases in costs, genomics currently plays a relatively niche role in healthcare, with clinical use largely limited to diagnosis of pediatric disorders or as a last resort in guiding cancer treatment. The Garvan Institute’s Kinghorn Centre for Clinical Genomics was one of the first sites in the world to acquire technology to sequence whole human genomes at scale. The service, now incorporated into spinout Genome.One, routinely sequences over 1,000 human genomes per month and is clinically-accredited for diagnostic testing of or predisposition to genetic disease. In addition to serving as a highly effective approach for diagnosing diseases that can be caused by large numbers of different genes, whole genome sequencing has potential for reanalysis in different contexts. This potential argues for a new testing paradigm, where genomic sequencing is undertaken once in an individual’s lifetime and analysed throughout their lifetime to guide clinical decision-making and optimise health management. Here I will present on our implementation, clinical accreditation and performance of whole genome sequencing in the routine diagnosis of genetic and rare diseases and its utility in personal health management and disease prevention. I will also discuss the challenges and opportunities for using genomic information to inform health at point-of-care, the incorporation of genomic information into medical records and its potential to transform medical research.