There was one time early on in my career when I had been gone from home continuously for 3 weeks on back-to-back assignments flying direct from one city to the next. I got a voicemail from one of the project managers saying they wanted me to go to some other city the next week, and this was right around the 4th of July holiday. (Meaning that to reasonably get to the assignment, I'd miss the holiday). This was the last straw.
I voicemailed him right back and cc'd my boss, with a "suggestion" that they try to find someone else to do it since I'd been on the road for so long. Result--I wasn't fired, and they found someone else to do it. It also seemed that mgt was much more sensitive to my travel schedule after that. Personally, I think that if you come to a tipping point, you should let someone know. If there is no realization that this is really a serious problem, then find a job elsewhere. This is easier said than done, but so is repairing a stress-related disease like high blood pressure or an ulcer.