Most will not be aware that it took a major accident to get any form of flight time limitations - I believe this was at Singapore in the late 1950s.
Around the time when I joined the airlines (1970) the Bader report into fatigue caused FTL limits to be revised. Before Bader a nights work could be Toronto-Montreal-Prestwick-Manchester-we would then ferry to London! After Bader we had to get off at Prestwick and a relief crew took the service onwards.
Although modern aircraft are more reliable with accurate autopilots etc my hallucination is that we are operating in a much less "user-friendly" environment. Just getting to the airport (and even the crew report point) on time having to fight the traffic can be a stressful experience. We are then faced with banal security checks etc. Rapid turnrounds with high traffic densities at airports which need more runways. Constant RT chat (what about controller fatigue too?) and multiple frequency changes due sectorisation and many heading and level changes. The list is endless - I love my job and the challenges I am faced with but my feeling with the fatigue issue is to be reminded of the Swiss Cheese model. We need all the holes to line up to create an accident and fatigue is one of those holes!
Human beings can work in "overload" for short periods quite successfully but when overload is the norm we are stacking up the odds for something to go wrong.