Clinical Genomics Uppsala (CGU) is a Swedish genomics infrastructure jointly set up by Uppsala University, Uppsala University Hospital and SciLifeLab with the aim to catalyze the transition of novel research findings into molecular diagnostics for clinical use. The unit is fully integrated within the Uppsala University Hospital and has extensive experience in development and implementation of state-of-the-art next-generation sequencing (NGS) technology in routine diagnostics. Long-read sequencing is now an established method with clear benefits for certain clinical genomic analyses including resolving complex structural rearrangements, large structural variant and repeats and analysis of genomic regions where methylation plays a role in the disease-causing picture. In this talk I will present some of the on-going long-read sequencing projects at CGU, where we are exploring how long-read sequencing can improve current diagnostic and prognostic genomic tests. I will present work including both national and local efforts with applications for rare diseases caused by complex chromosomal rearrangements and repeat expansions as well as for hematological malignancies commonly caused by acquired translocations, inversions, insertions and/or deletions.