The language barriers: Italian director Sergio Leone didn't speak a word of English, and two of the American stars didn't speak a word of Italian. This left Eastwood (The Good) to use a translator and Wallach (The Ugly) to use French (as he and Leone were both fluent) to communicate with their director. But inarguably the biggest problem that arose due to different languages being spoken came from the Italian fluent crew and one Spanish speaking trigger man.
The problems the language barrier presented: In the movie there's a scene where a bridge gets blown to kingdom come. The Italian crew gave the honor of igniting said blast to one of the Spanish soldiers who were standing in for the American Civil War soldiers. While everyone was waiting around for the sky to be just right, a member of the effects crew said a word over the radio that sounded like the cue for the soldier (who was listening through a language he didn't understand for that one word), and he subsequently blew the bridge to kingdom come with not one single camera rolling.
The solution: The bridge was rebuilt, and they blew it all to hell a second time.