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The 16th century is defined by the calendar of Earth as occurring from the year 1501 through the year 1600.
- The T-Rogorans conquer the Skrreea. They kill most of the Skrreean leaders, and force the rest of the population to work as laborers and servants. (DS9: "Sanctuary")
- The Second Dynasty rules over the Klingon Empire, but ends with General K'Trelan assassinating Emperor Reclaw then later putting to death all the members of the Imperial Family. The next ten years that followed, the Empire was ruled by a council elected by the people, which is referred to as "The Dark Time" by Klingon historians. Following this period a new group of Klingons, called the Third Dynasty, were given the titles and names of the original Imperial Family in order to create the illusion of an unbroken line since the true Imperial bloodlines were cut at the end of the Second Dynasty. (DS9: "You Are Cordially Invited")
- According to Q, in this century, Humans are fighting each other over "tribal god images". (TNG: "Encounter at Farpoint")
- Autopsy reports relevant to duels over a woman going as far back as this year are later included in The Doctor's database. (VOY: "Parturition")
- In western Europe, early experiments with the optical microscope are made. Sketchbooks and other forms of art of the time record early observations of a more or less scientific nature, as seen during Captain Janeway's Leonardo da Vinci holodeck program. (VOY: "Scorpion", "Concerning Flight")
|15th century||Timeline||17th century|