A long war between the Federation and Cardassians.
The Federation and the Cardassian Union fought a long series of conflicts over their border in the mid-twenty-fourth century. One of the worst events was the Cardassian attack on the Federation outpost at Setlik III in 2347, where many civilians were killed. Captain Benjamin Maxwell lost his wife and children there, and Miles O'Brien, then serving under Maxwell on the USS Rutledge, fought in the defence.
An armistice was reached in 2366, and in the Next Generation episode The Wounded, Maxwell attacks Cardassian ships on his own, convinced they are preparing for another war. Picard stops him, though the episode suggests his suspicions were not entirely wrong.
A treaty in 2370 set a new border and created a Demilitarised Zone, which left some Federation colonies on the Cardassian side. Many colonists refused to leave, as shown in Journey's End, and some formed the Maquis, a resistance group that fought the Cardassians and later drew Starfleet into conflict as well.