Clinical metagenomic next-generation sequencing (mNGS) is the comprehensive analysis of microbial and host genetic material (DNA or RNA) in samples from patients. It uses the techniques of metagenomics for the identification and genomic characterization of bacteria, fungi, parasites, and viruses without the need for a prior knowledge of a specific pathogen directly from clinical specimens. The capacity to detect all the potential pathogens in a sample makes metagenomic next generation sequencing a potent tool in the diagnosis of infectious disease especially when other more directed assays, such as PCR, fail. Current limitations include clinical utility, laboratory validity, sense and sensitivity, cost and regulatory considerations.