The still recent field of metagenomics emerged due to the cost effectiveness and other advances in high throughput sequencing and associated technologies. The ability to probe the previously unexplored compositional and genomic diversity of microbial communities, or microbiomes, spawned a number of new fields such as human microbiome research. While the sequencing technologies continue to evolve and new technologies emerge, and as metagenomic sequencing continues to be applied to a broader range of samples to address increasingly diverse sets of scientific questions, similar advancements both upstream and downstream of the sequencing of microbiomes have become research priorities. Some advancements in bioinformatics methods being worked on at LANL will be presented, together with their application in the detection if infectious diseases from clinical samples, and the study of microbiomes. Preliminary work exploring appropriate culturing conditions upstream of sequencing, and challenges that remain in standardized analysis and processing of metagenomic data will also be discussed.