One of the grand challenges is biology is to understand the patterns of evolutionary diversity and ecological roles for the vast unseen “creatures” that inhabit our planet. In the late 1980s the advent of the polymerase chain reaction (PCR) transformed molecular evolution. At the same time Allan Wilson’s lab was investigating well known fundamental questions in evolutionary biology, including our own origins it also played a major role in developing PCR based applications in population genetics and systematics. Among the most impactful was a simple demonstration in 1989 that a single pair of common PCR primers could be used to amplify homologous regions of mitochondrial genomes from diverse animals. That methodology ultimately transformed population biology and gave rise to modern day meta-barcoding. In my group we have used these technologies to explore the patterns of diversity in the small eukaryotic phyla, and most recently applied those approaches to investigate the consequences of the Deep Water Horizon Oil Spill in the Gulf of Mexico. We now have the opportunity to apply those same approaches coupled to Next Generation Sequencing in an attempt to test for the existence of ecologically meaningful patterns of biogeographic structure among these small organisms long thought to be largely unstructured.