The film: A 1995 adaptation of the ill-fated Apollo 13 flight, which midway to the moon suffered an explosion that forced the crew to abort its lunar landing and return home before running out of oxygen.
The line: "Houston, we have a problem."
The setup: Delivered by astronaut Jim Lovell (Tom Hanks). The line was based on Lovell's radio transmission during the 1970 flight, though Lovell's version — "Houston, we've had a problem" — was slightly different.