It was the last major outbreak of bubonic plague in Britain that killed almost one quarter of London's people within 18 months.
For the time time, the strand of bacteria that is believed to have caused the Great Plague in 1665 has been identified.
Scientists in East London have found Yersinia pestis -- thought to be behind the Black Death centuries earlier -- in skeletons that were discovered during excavation work on an underground rail link beneath London.
The bacteria was discovered in the teeth of five of the individuals -- an effective time capsule that preserves the genetic information of any bacteria lurking in a person's bloodstream at their time of death.
About 3,500 burials have been uncovered during excavation of the site.
Researchers are optimistic the findings will likely shed new light on the swift spread of the plague.
"It (the bacteria) does not behave that way today. It's much slower and spreads less dramatically," senior osteologist at the Museum of London Archaeology Don Walker said.
"Could it be that there was some form of mutation? Or was it to do with host susceptibility and response?"
So, what next?
The sequence of DNA from the 1665 outbreak will be compared with that recovered from the 14th century Black Death to understand the evolution the disease -- and the lifespan of the individuals themselves.
"We want to know if there was a local/European plague focus -- a reservoir of the disease within a rodent population -- or whether there were separate waves of plague coming from Asia.
"Current evidence suggests the former."
The identification also marks the 350th anniversary of the Great Fire of London that swept through the city in 1966 -- another vital piece of the puzzle that many accredit to wiping out the plague once and for all.
For now, all it comes down to is the DNA.