The Shermans were brought onto the film by Walt Disney due to Disney's feeling that the interpretation was keeping too true to the Rudyard Kipling book. In a deliberate effort to keep the score "light", this song as well as the Sherman Brothers' other contributions generally concern darker subject matter than the accompanying music would suggest. "Trust in Me" originated from Disney's suggestion to add a song to Kaa's sequence, and was written by Shermans based on "The Land of Sand", a song they had composed for 1964's Mary Poppins but ended up not being used. Kaa speaks and sings with a subtle, lilting lisp giving the song a humorous dimension that it would not otherwise have.
In Series 22 Episode 3 of Top Gear, Jeremy Clarkson makes a brief humorous reference to the song during a sequence in which he comes face to face with a mannequin's genitals.
In an episode of Not Going Out, Daisy tells Lee that Lucy is falling under the spell of her old boyfriend Scott, like Kaa hypnotizing Mowgli. She imitates Kaa singing "Trust in me", though Lee thinks she's acting like Hannibal Lector.
In Jon Favreau's 2016 live action version of the 1967 Disney animation Scarlett Johansson, voicing the role of Kaa, hypnotically hisses "Let go of your fear now....and trussssssst in meeeeeee". Hinting at the song's inclusion.