This work represents an update of knowledge regarding the detection methods for human microbiome-associated archaea. Despite the fact that, during the last three decades, only four methanoarchaeal species have been isolated from the human mucosa, including faeces, subgingival plaque, and vaginal mucosa (Methanobrevibacter smithii, Methanosphaera stadtmanae, Methanobrevibacter oralis and, most recently, 'Methanomassiliicoccus luminyensis'), molecular studies, including PCR and metagenomic analyses, have detected DNA sequences indicative of the presence of additional methanoarchaea, as well as non-methanogenic archaea, in the human intestinal tract. Opinion is divided on the roles (if any) of these organisms in human disease, and certainly the data are still unclear. Future research and recently reported data highlighting the antimicrobial susceptibility of the human methanoarchaea could help in the design of selective media to discover additional human mucosa-associated archaea and ascertain their role in human infections involving complex flora.