Buck Taylor, who played Newly, was also requested by Jack Lord for the role of Dan "Danno" Williams on Hawaii Five-O (1968) at the same time he was up for the role of Newly O'Brian.
In the radio series, Kitty Russell was a madam for prostitutes. In the first couple of seasons, there were some hints at that on the TV series. James Arness explained on the DVD commentary that after the first couple of seasons, they decided to drop those references to make the show more family friendly, and so Kitty became just a lady saloon owner.
Dennis Weaver was the first actor cast. Weaver said on the DVD commentary that he knew they were leaning towards James Arness for Matt, but he was in the Bahamas at the time filming a movie with John Wayne. They went ahead and started casting the other parts, so he ended up being the first one officially chosen for the TV series.
Kitty Russell: Matt, you can't account for everything that happens to people who touch you. You know, I learned a long time ago, there are some things in this life that you just accept the way they are.
Dr. Galen 'Doc' Adams: [Festus offers to buy Doc a beer with a silver dollar that he earned from shoeing horses in episode "Whelan's Men".]
Why don't you take that money and invest it in something? Why don't you do that?