Kelsey Grammer used an acting method that he called "requisite disrespect." He would rehearse each scene only once, and he would not learn his lines until a few moments before each scene was shot. Grammer felt that his method brought energy and realism to his performance. The cast and crew got used to it, but guest stars did not like his method.
David Hyde Pierce has said prior to this series, he had no strong interest in wine nor opera. John Mahoney, whose Martin Crane character eschews anything cultured, introduced Pierce to both.
Moose (the original Eddie) was fourteen when this show ended. His fur had turned snow white and he was almost completely deaf, but his trainer carried him out on-stage after the final episode was recorded so he could take his bows with the rest of the cast. David Hyde Pierce later said that it was one of the most moving moments of the evening, watching Moose recognize and react to the applause one last time.
The two final choices for the role of Roz were Peri Gilpin and Lisa Kudrow. Kudrow was originally cast, because her line readings were funnier. But during rehearsals, the show's creators felt that Kudrow lacked the forcefulness needed to play Roz, and she was replaced with Gilpin.
The series was originally going to cast an actress to portray Niles' (David Hyde Pierce's) wife Maris, but after the first couple of seasons, the writers found they had too much fun writing her as an unseen character, and as the descriptions of her became more outlandish and contradictory, they felt finding the right actress would be close to impossible.