Microorganisms play crucial roles in nearly every ecosystem, from the human body to the soil and sea. Metagenomics and related high throughput DNA sequencing techniques, have given us a first glimpse of our invisible and unculturable friends, leading to the recent discovery of dozens of new phyla. Meanwhile, population genetics and genomics have been powerful tools to understand the ecological and evolutionary forces governing organisms. To date, it has been very difficult to apply population genomics approaches to microbes due to limitations inherent in DNA sequencing technology. I will describe recent work by my group and others to develop novel sequencing technologies and corresponding statistical methods to enable population metagenomics, and will discuss possible applications to clinical diagnostics and microbial ecology.