A pandemic is a disease that effects people over an extensive geographical area (from Greek pan+demos, all+people). There have been a number of significant pandemics in human history, all of them generally zoonoses that came about with domestication - such as smallpox, diphtheria, influenza and tuberculosis. There have been a number of particularly significant epidemics that deserve mention above the 'mere' destruction of cities:
Peloponnesian War, 430 BCE - An unknown agent killed a quarter of the Athenian troops and a quarter of the population over four years. This fatally weakened the dominance of Athens, but the sheer virulence of the disease prevented its wider spread.
Antonine Plague, 165-180 - Possibly smallpox brought back from the Near East; killed a quarter of those infected and up to five million in all. At the height of a second outbreak (251-266) 5,000 people a day were said to be dying in Rome.
Plague of Justinian, started 541 - The first recorded outbreak of the bubonic plague. It started in Egypt, reached Constantinople the following spring, killing (according to the Byzantine chronicler Procopius) 10,000 a day at its height and perhaps 40 per cent of the city's inhabitants, and went on to destroy up to a quarter of the population of the eastern Mediterranean.
The Black Death, started 1300s - eight hundred years after the last outbreak, the bubonic plague returned to Europe. Starting in Asia, the disease reached Mediterranean and western Europe in 1348 (possibly from Italian merchants fleeing fighting in the Crimea) and killed twenty million Europeans in six years, a quarter of the total population and up to a half in the worst-affected urban areas.
Cholera, first pandemic 1816-1826 - Previously isolated to the Indian subcontinent the pandemic began in Bengal then spread across India by 1820. It extended as far as China and the Caspian Sea before receding. The second pandemic (1829-1851) reached Europe, London in 1832, New York in the same year, the Pacific coast by 1834. The third pandemic (1852-1860) mainly affected Russia, with over a million deaths. The fourth pandemic (1863-1875) spread mostly in Europe and Africa. The sixth pandemic (1899-1923) had little effect in Europe because of advances in public health, but Russia was badly affected again. The seventh pandemic began in Indonesia in 1961, called El Tor after the strain, and reached Bangladesh in 1963, India in 1964, and the USSR in 1966.
Influenza, 1918-1919 - Beginning in August 1918 in three disparate locations - Brest, Boston and Freetown the disease spread across the world killing twenty-five million in all - an estimated 17 million in India, 500,000 in the USA and 200,000 in England. It vanished within eighteen months, and the actual strain was never determined.
The epidemic disease of wartime was typhus, because of this it was called Camp Fever. Emerging during the Crusades, it had its first impact in Europe in 1489 in Spain. During fighting between the Spanish and the Muslims in Granada, the Spanish lost 3,000 to war casualties and 20,000 to typhus. In 1528 the French lost 18,000 troops in Italy and lost supremacy in Italy to the Spanish. In 1542 30,000 died of typhus while fighting the Ottomans in the Balkans. The disease also played a major role in the destruction of Napoleon's grande armée in Russia in 1811.
Encounters between European explorers and populations in the rest of the world often introduced local epidemics of extraordinary virulence - The entire native (Guanches) population of the Canary Islands in the C16; Half the native population of Hispaniola in 1518 through smallpox; Smallpox also ravaged Mexico in the 1520s (killing 150,000 including the emperor in Tenochtitlan alone) and Peru in the 1530s, adding the European conquerers; Measles killed a further two million Mexican natives in the 1600s; As late as 1848-49 as many as 40,000 out of 150,000 Hawaiians are estimated to have died of measles, whooping cough and influenza.
There are also a number of unknown diseases that were extremely serious but have now vanished and the etiology of the disease cannot be established. Examples include the previously mentioned plague in 430 BCE Greece and the English Sweat in sixteenth-century England which struck people down in an instant and was more greatly feared even than the bubonic plague.
Diseases that may attain pandemic proportions include Lassa fever, Rift Valley fever, Marburg, Ebola and Bolivian haemorrhagic fever. But currently the recent emergence of these diseases into the human population means their virulence is such that they tend to 'burn out' in geographically confined areas, or that their effect on humans is currently limited. AIDS can be considered a pandemic but it is currently most extensive in southern and eastern Africa and is slow to spread.