Darwin's monkey "Wallace" is a reference to the naturalist Alfred Russel Wallace who independently developed the idea of natural selection. Darwin and Wallace presented the theory together, but due to the publication of "On the Origin of Species" Darwin usually gets sole credit for the theory. The scene on Butterfly Island when Darwin closes Wallace in the sack and says " we.... I have an idea" alludes to him taking sole credit for ideas that were not completely his own.
A miscommunication between the casting agent and Catinca Untaru led her to believe that Lee Pace was a real-life paraplegic. Director Tarsem Singh found that this brought an added level of believability to their dialogue, so he decided to keep almost the entire cast and crew under the same impression. Singh had to speak to the actor playing Alexandria's father and explain that his role was smaller than it appeared, since the script implied that he played the role of the bandit (actually played by Pace) in the fantasy scenes. Apparently it was hard to keep up the lie - a makeup artist walked into a room to find Pace standing and almost passed out from shock.
The director claims that there are no visual effects in the film despite its surreal looks. Everything was shot on real locations. However, there are about a dozen people credited as visual effects in the credits.
One of the significant plot developments - Alexandria's misinterpreting the letter E as the number 3 in a note written by Roy - was derived from an accidental misreading by the 6 year old actress during filming, which the director then realized he could adapt into a clever twist in the story.
Singh shot the hospital scenes with Catinca Untaru in chronological order. As filming progressed over the course of six weeks, she grew taller and her English improved, like her character would have in real life. She also lost her two front baby teeth right before shooting began, so filming in sequence allowed for the continuity of the gap between her teeth to remain consistent.
Apart from the movie poster based on the Salvador Dali painting, the mask on the face of the bandit (which is shown on the face of the girl as well on multiple occasions) could also be a tribute to the same painting.