At the height of his power, in the third century BCE, and with an empire that stretched from Southern Europe to West Asia, Alexander the Great suddenly took ill and died.
For many years it has been a "great" mystery, but fortunately for us the Greeks were assiduous record keepers and the events surrounding Alexander's death are documented in the Royal Diaries, which were written by the Greek historian Arrian. Things started getting bad when Alexander got really wasted. According to Arrian:
Alex "was drinking far into the night with some friends...Some state that he wanted to leave the drinking party and go to bed, but then Medius met him, the most trusty of his companions, and asked him to a party, for he promised that it would be a good one. [Alexander] drank and caroused with Medius. Later he rose, had a bath and slept. He then returned to have dinner with Medius and drank far into the night. Leaving drinking, he bathed, after which he had a little to eat and went to sleep there."
Following this, Alexander became afflicted with a terrible fever, tremors, and weakness. He was dead in less than two weeks. The popular and most fun explanation was that Alexander died from alcohol poisoning complications after imbibing way too much ancient wine (a harsh beverage, no doubt). But scholars note that there are no records of vomiting tied to his illness. Vomiting is a tell-tale sign of alcohol poisoning.
According to Wikipedia, there are still many competing conjectures as to the actual cause of death, and it is not even established whether or not there was foul play involved. One argument against poisoning is that poison would kill quicker, and Alexander was sick for twelve days before he died. If it wasn't poisoning, then there are a host of different afflictions that it could have been including meningitis, typhoid, and west nile virus. Some, though, insist that Alexander's life of heavy drinking may have finally caught up with him--whatever the actual cause of death may have been.