This chapter is about pandemics, a somewhat ambiguous term, defined in the Oxford English Dictionary as ‘a disease prevalent throughout a country, a continent, or the world’. In present modern usage the term takes greater cognizance of its original Greek derivation and is largely restricted to global prevalence (pan demos) – all people. The same source tells us that ‘plague’ has a broader meaning, implying a sudden unexpected event that is not necessarily a disease, but introducing the concept of acute, lethal, and sudden danger – characteristics that are connoted but not specifically denoted by the term ‘pandemic’. It will become apparent that glimpses of the future must consider the emergence of new pathogens, the re-emergence of old ones, the anthropogenic fabrication of novel agents, and changes in the environment and in human behaviour. In other words ‘the problem’ in addressing infectious disease threats is not one but many separable problems, each of which must be isolated in traditional scientific fashion and separately evaluated as components of what I like to call ‘holistic epidemiology’. This emerging discipline comprises microbial and human genetics, human behaviour, global ecology, toxicology, and environmental change. As we leave our mothers’ wombs and enter this vale of tears (and sometimes before) we are invaded by microbes that may become our lifelong companions, profiting from this intimate relationship by the food and shelter that our bodies offer. They, in turn, often provide us with nutrients or vitamins derived from their own metabolic processes and may even immunize us against future assaults by related but less kindly microbes. In other words, we and they (usually) coexist in a state of armed neutrality and equilibrium. But humans bear a chronic burden of infectious diseases. Included in this burden are some diseases that have demonstrated a capacity to break out in pandemic form, depending on the circumstances that are defined later. The less overt contributors to human misery will be briefly reviewed before discussing the nature of the acute aberrations that comprise the more dramatic pandemics and plagues that suddenly burst forth in a catastrophic manner.