Diseases date back to the dawn of humankind. As humans have evolved, so too have their diseases: some that were once rare have become common, others have disappeared and new varieties have emerged. Many of these changes have taken place in the wake of important transformations in human civilizations and ecology. It is therefore feasible to propose that diseases succeed and fail in response to humanity’s advances. My hypothesis to explain the appearance and disappearance of some of these diseases—both infectious and chronic—is that changes in human ecology result in changes in the microbes that populate our bodies. This, in turn, affects our physiology and ultimately our health. The invention of agriculture about 10,000 years ago led to a massive increase in the human population, but at a price: by living in closer proximity to domesticated animals and those that parasitized their food supply (such as rats), humans became more susceptible to measles, plague, tuberculosis and other zoonoses. Urbanization during the Middle Ages was one of the main factors facilitating the devastating spread of Yersinia pestis through the crowded cities of Europe—the Black Death subsequently killed about 30% of the continent’s population. Improved hygiene in the nineteenth century eventually reduced the prevalence of plague, along with cholera, dysentery, materno-fetal mortality, childhood infections and other ancient foes. The agricultural revolution after the Second World War relegated famine and its associated diseases—such as pellagra, which is a deficiency of niacin—to history, at least in the industrialized world. In the nineteenth and twentieth centuries, industrialization—and the scientific revolution that preceded and facilitated it—also gave humans new tools for controlling infectious diseases. Due to improvements in sanitation, antibiotics and vaccines, smallpox has now been eradicated, polio is on the brink of extinction and many other infectious diseases are on the decline. However, industrialization also made possible the rise of new diseases (Table 1). Chronic ailments, such as allergies, asthma, coronary heart disease and cancer, are taking a major toll in developed countries. Man-made toxic compounds affect our immune, neurological and reproductive systems. Predictably, as humans move through a ‘post-modern’era, different diseases are becoming prominent. For some, such as HIV/AIDS, the cause is obvious: in this case, the introduction of a new microbial agent into a population that has no immunity against it, and its dissemination through both ancient and modern routes of transmission, namely sexual activity and needle sharing. For many other post-modern diseases (Table 1), the aetiology is more obscure; however, I postulate that changes in the ecology of our indigenous microbiota have important roles in their emergence. This view parallels the well-known hygiene hypothesis, which posits that diminished exposure to parasites and pathogens early in life—through improved hygiene, vaccines and antibiotics—might be partly responsible for an increased prevalence of allergic and autoimmune disorders in later years (Strachan, 1989; Cookson & Moffatt, 1997). The lack of pathogenic and invading organisms might cause the immune system to shift its immunological response away from a balance between type 1 and type 2 T-helper cells to one skewed towards the latter