Chlamydia trachomatis is the most widely disseminated bacterial sexually transmitted infection and a leading cause of pelvic inflammatory disease and infertility. The last five years have witnessed a technological revolution in the analysis and characterisation of the function of chlamydia virulence factors and how they modulate host cellular functions. As a result, we are gaining unprecedented insights into the mechanisms underlying chlamydia-mediated inflammation and tissue damage as well as learning how chlamydia adapts to the human host environment. Prominent among these new technologies are methods to perform genetic and molecular genetic analysis in these bacteria, which until very recently were considered to be “genetically intractable”. I will review some of the key developments in the emerging field of chlamydia genetics and provide examples of how these approaches are leading to the discovery of new virulence factors and strategies used by this pathogen to modulate innate immune responses. Finally, I will discuss recent progress in how these molecular genetic approaches are being used for the design of new vaccines and to better understand adaptive and innate immune responses to chlamydia infections.