The Colonies are areas of North America that have been contaminated by pollution and radioactive waste. The Republic of Gilead often sends those convicted of various crimes, known as Unpeople, to the Colonies, to help clear them up as punishment. The Colonies are known to have horrific living conditions, with prisoners or Unpeople sent there being used as slave labour. Those sent to the Colonies often die quickly from sickness brought on by the pollution and poor living conditions, and from malnutrition and over-exertion. Being sent to the Colonies is regarded by many as a fate worse than death, and the mere mention of them can instill great dread in the characters.

Notably, after being shown a video of the Colonies, the once-rebellious and outspoken Moira chose to become a prostitute at Jezebel's rather than be sent to the Colonies. Some women who were convicted of serious crimes, such as being an intellectual or 'Gender Treachery' (homosexuality), but were still fertile, willingly chose to become Handmaids over being sent to the Colonies. It is mentioned that Handmaids that fail to conceive are eventually declared Unwomen and sent off to the Colonies, leading many Handmaids to take risky measures in an effort to get pregnant and be spared such a fate.

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