When one understands that the "rat race" is not going to give him happiness.
These "high profile" jobs seem good only to an outsider, but any objective viewer will understand the stress that comes along with the high pay. I sometimes felt sorry for management people working in the company I worked for because they were always under so much pressure from upper management. Something went wrong, they were answerable. They did not do the mistake. Someone, much lower down the chain of command did some stupid mistake and they felt the wrath.
You are just a ROI (Return on investment) calculation for your company. You see that you are nothing but a "resource" for your company. They don't care about you as a person. Even if they show as if they care for you as a person, there is a ROI calculation even for that gesture. How long can a sane, observant man handle being treated like a resource?