In the pilot episode, Emissary, a stable wormhole to the distant Gamma quadrant is discovered and Deep Space Nine is repositioned at its portal. Deep Space Nine and Bajor then occupy a major strategic position in opening up a whole new region of space for exploration and colonisation. At first the Gamma Quadrant looks to be an interesting new oportunity for Bajor and the Federation, but gradually a menace appears in the form of a powerful empire known only as "The Dominion".

The second season ends with a serious skirmish with soldiers of the Dominion, the feared Jem Ha'dar.

In The Search, the first episode of the third season, Starfleet promote Sisko to Captain and station a prototype warship called "The Defiant" at DS9. As a result of an agreement with the Romulans, the Defiant is equipped with a cloaking device (the only Federation craft to have one!). It soon becomes clear that the rulers of the Dominion, the Founders are none other than Odo's people - the changelings.

In season four, in the season premiere episode The Way of the Warrior, Klingons reemerge as a threat when they use the threat of Dominion attack as an excuse to send a fleet to DS9 to stop and search ships going through the wormhole.

Worf joins the crew and finds out that the Klingons are about to invade Cardassia. When Sisko rescues the new civilian government of Cardassia, the Klingons attack DS9 and Chancellor Gowron terminates the Federation-Klingon alliance!

Although the Klingons are forced to withdraw from most of Cardassian space, they retain some of the systems they've taken near Bajoran space and periodically threaten DS9 and the wormhole.

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