When the film was screened at the Sundance Film Festival, all tickets were sold out, and some people watched it standing because they did not buy reserved seats.

Director Katsuhiro Ôtomo describes the film as a fable: "The film doesn't have a real climax, it calmly moves toward its end. But that too is very much like our lives as human beings. If you look back at your life, maybe you can point to moments that you feel were a climax or a turning point, but when they actually happened you didn't experience them the same way. Life moves ahead quite calmly and gradually, and I wanted to bring that same feeling to Mushishi."

Ginko's title of "Mushishi" means, literally, "bugmaster"; "mushi" means "bug" (as the Mushi are supernatural parasites), and "shi" means "master" (as in "expert" or "doctor").

Katsuhiro Ôtomo sent a copy of the script to "Mushishi" creator Yuki Urushibara for review, but she allowed him to have complete creative control over the film as a sign of her faith in him.

Katsuhiro Ôtomo decided to adapt "Mushishi" as he saw it as "an opportunity to mix live action and computer graphics, to create a hybrid of the natural and the virtual."

The writers found the episodic nature of the "Mushishi" saga challenge in adapting it into a film. They however were able to fashion a cohesive screenplay by combining elements of the different stories in Mushi-Shi (2005): Tender Horns - a child has horns growing on his head Raindrops and Rainbows - a man is in pursuit of a Mushi in the shape of a rainbow A Sea of Writings - a Mushi paralyzes a girl to make her write scrolls about Mushi One-Eyed Fish - Genko's origin, and a female Mushi adopts a child (in the manga/anime the child is a stranger, but the film makes it Ginko's mother).