Genome sequencing in medicine has revolutionized clinical and basic research, disease diagnostics in particularly of rare diseases and cancer, and is fundamental for personalized treatment approaches. Novel long-read sequencing (lrGS) technologies overcome the limitation of conventional sequencing and allow the identification of structural variants and genomic regions that were previously inaccessible. While lrGS technology is already integrated as part of genome diagnostics in some centres in Europe, its full potential in terms of diagnostic sensitivity and specificity and in different disease cohorts still needs to be widely explored in clinical routine. Thus, a European long-read initiative (ELRIN) was formed by human genetic institutes across Europe to develop new standards for ONT-based lrGS technology, to clearly define its advantage compared to srGS and to generate novel reference data sets. The ELRIN consortium serves as expert panel for clinical questions and collaborates closely with networks such as ERDERA or The Genome of Europe initiative. With these approaches, ELRIN aims to explore the full potential of lrGS in genomic diagnostics to be integrated as a first-line diagnostic tool in clinical patient care in the near future.