Conservation genomics has increasingly transitioned from a promising concept to a science that integrates a range of advanced analytical approaches, providing new insights into inbreeding, genetic load, demographic history and adaptive divergence in species of conservation concern. Yet, questions remain about how effectively these advances translate into practical conservation action. This Special Issue, Conservation Genomics-Making a Difference, brings together 37 papers that collectively assess how genomic data are contributing to conservation science and management. The contributions encompass empirical studies, reviews, and perspectives that together demonstrate how genomic tools are now used to identify management units, quantify inbreeding, analyse inbreeding depression, reveal adaptive variation, forecast genomic vulnerability under climate change, and guide genetic rescue and assisted migration. Several papers show direct integration of genomics into conservation planning, including fisheries management, guiding restoration of endangered or habitat-forming species, and monitoring of genetic indicators under the Convention on Biological Diversity. Others highlight emerging questions in conservation, such as the significance of structural variation, and the genomic basis of invasiveness. However, persistent challenges remain, notably in bridging the gap between research and policy, uneven global distribution of genomic resources, and translating complex analyses into practical management advice. Nevertheless, the advances presented in the 37 papers show that conservation genomics is moving beyond its early theoretical and technical focus towards real-world applications. The field is maturing and is increasingly fulfilling its promise to make a real difference for populations, species, and ecosystems.