Since the advent of next-generation sequencing (NGS) technologies, the untargeted screening of samples from outbreaks for pathogen identification using metagenomics has become technically and economically feasible. However, various aspects need to be considered in order to exploit the full potential of NGS for virus discovery. Here, the authors summarise those aspects of the main steps that have a significant impact, from sample selection through sample handling and processing, as well as sequencing and finally data analysis, with a special emphasis on existing pitfalls.