realize that many of your 'dreams' won't happen. You'll never be wealthy, own the beach house, or have the starting QB son. You maybe made a couple dumb career choices, or didn't invest enough when you were in your 20s etc. and that's when the depression/regret/frustration sets in. The realization that your life isn't going to turn out like you pictured it turning out is a tough realization. (Not to mention the more important components of life including marriage, relationships that aren't what you wanted them to be etc.)

I've seen it with a few friends and it causes real issues with depression. Suddenly you wake up at 55 and realize 'it' isn't going to happen for you (whatever 'it' was to begin with).