Jane Seymour is British. In fact, she used to be a Bond Girl. It's not exactly clear whether Quinn's accent is supposed to be some version of upper-class Bostonian; her family talks roughly the same way.
Cloud Dancing, a Cheyenne shaman, is played by Osage/Cherokee and Lakota actor Larry Sellers.
Killed By Request: Averted at the last minute when Joe Lando wanted to leave after the 5th season, so it was planned that Sully would die falling down from a cliff. But a massive backlash from the fans made it necessary for everybody to re-think this decision. So in the end, Sully survived. But to make a compromise with Joe Lando, he was free to only appear in half of the episodes in the 6th season (which also turned out to be the show's last).
Midway through the show, actress Erika Flores was replaced by Jessica Bowman as Colleen. Apparently, Flores had a contract dispute. Due to a difference between production order and airing order, the old actor reappears in one story after the new one takes her place.
And several actors were swapped out after the pilot, including Colm Meaney as Jake Slicker.
Michaela's mother was originally played by Jane Wyman, who was later replaced by Georgann Johnson. Johnson stayed in the role for the remainder of the series.
Teresa was played by Michelle Bonilla in Season 5, Alex Meneses in Season 6
Promoted Fanboy: When Fred Rogers mentioned in an interview that Dr. Quinn was one of the few TV shows he enjoyed watching, the producers arranged for him to become a Guest Star. He played the role of "Reverend Thomas", his only on-camera appearance as a fictional human character.
John Schneider had a guest role in the first season as a fugitive bank robber before being cast years later as Sully's best friend/new sheriff Daniel.
James Leland Adams played General Custer in several episodes before being cast as the pompous Preston A. Lodge III.
Brandon Douglas played a con artist before being cast as neophyte physician Andrew Cook.
Alley Mills can be glimpsed as one of Hank's prostitutes shortly before playing Mike's sister Marjorie.
Black Hawk, the Cheyenne beside Chief Black Kettle in the pilot movie, is retooled into Cloud Dancing following after CBS greenlit the production of a full series. The differences are that Cloud Dancing can speak English whereas Black Hawk could not, and Cloud Dancing had a much more prominent role in the show as opposed to Black Hawk being just another face in the crowd of extras.