Initially developed for high-consequence viruses like Ebola, the ARTIC protocol proved crucial during the COVID-19 pandemic, facilitating rapid SARS-CoV-2 sequencing and global dissemination. For ARTIC 2.0 we will broaden the scope considerably to include endemic human pathogens, arthropod-borne viruses and zoonotic viruses as well as challenging new threats like the spread of AMR. We will enhance our ability to conduct responsive investigations of unusual or concerning changes in the pattern of infectious disease anywhere in the world, by leveraging new tools such as metagenomics. This could be a cluster of hemorrhagic fever of unknown aetiology but equally a spike of incidence in a known endemic arbovirus or childhood viral disease like measles. What links these events is that the investigations have to be sufficiently rapid that the information acquired can lead to effective response. ARTIC 2.0 is creating a fully equipped toolbox where a robust, low-cost and accessible set of tools, that make use of the same equipment, reagents and bioinformatics, are ready to be rapidly applied to a wide range of investigations guided by an extensive knowledge base and flexible analysis pipelines.