The film was shot in 28 countries, over the course of four years. According to the director no stages or sets were ever used, only existing locations.
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.
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 several 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.
According to his Facebook profile, Peter Jackson decided to cast Lee Pace as King Thranduil in the 'Hobbit' trilogy after seeing his performance in this movie.