A broad chronological overview of the plagues of the past and the present provides a basis for understanding how they have arisen, how they have affected societies over time, and how humanity has responded to the challenge of each new wave of deadly disease. Many puzzles still surround the plagues of antiquity, although recent techniques such as DNA analysis of skeletal remains are beginning to provide clues as to their causes; it has, for example, now been confirmed that the plague bacillus, Yersinia pestis, was responsible for the ‘Black Death’ of the mid-14th century. Many other infectious diseases or ‘plagues’, such as smallpox, typhus, cholera and influenza, have afflicted human populations over the centuries. As the causes of these diseases have become increasingly well understood, humanity has devised ever more effective means for their control. With the extension of human lifespan that has resulted from such progress, other medical conditions have become increasingly common, notably the neurological disorder, Alzheimer's disease. Although not infectious, this disease has become so prevalent in recent years that it is has been called a ‘21st century plague’. The intrinsic origins of this highly debilitating condition are now being explored intensively by scientists from many different disciplines leading, as with the plagues of the past, to new ideas as to potential strategies for its prevention and treatment.