The study of diseased invertebrates dates back to ancient times. Aristotle in his Historia Animalium used his observational ability to describe a disease of bees; presumably those used by the ancient Greeks to produce honey. Observation, be it with the naked eye or with the assistance of microscopes, still remains a fundamental part of any disease diagnosis even over 2000 years after Aristotle died in 322 BC. The last 50 years have seen a renaissance in the study of invertebrate diseases aided by advances in microscopy, microbiology, biochemistry and the advent of molecular biology. Most recently, the development of so-called high throughput sequencing has resulted in fundamental changes in our understanding of disease states including their polymicrobial aetiology and pathobiomes. There are two aims to this chapter: (1) to provide an overview of the techniques available and (2) review recent developments in high throughput sequencing (HTS) and how this is influencing our understanding of disease processes.