All SFX were filmed live, with no post-production. For example, to achieve the famous 'shaking head' effect, director Adrian Lyne simply filmed the actor waving his head around (and keeping his shoulders and the rest of his body completely still) at 4fps, resulting in an incredibly fast and deeply disturbing motion when played back at the normal frame-rate of 24fps.
Certain imagery was inspired by the photographs of Joel-Peter Witkin. Most recognizably, the image of the hooded, legless man shaking his head is inspired by Witkin's 1976 photograph "Man With No Legs".
The Bergen Street station in the film was actually an abandoned, lower level portion of the station, which had to be re-tiled and fixed to look as if it was still in working condition.
All ads in the subway and Bergen Street station are anti-drug ads.
Adrian Lyne turned down directorial duties on The Bonfire of the Vanities (1990) so he could direct Jacob's Ladder. His first choice for the role of Jacob Singer was Tom Hanks, but, by coincidence, Hanks turned down the film so he could make The Bonfire of the Vanities.