When do y'all decide your bike has had enough; time to let it loose in on the great road in the sky?
Do you wait until the frame cracks or folds, or do you come to a point where you don't trust it any more?
Do you ride your bike until it's a pile of dust and moldering parts, or get bored with it first and replace it with something newer and nicer?

{edit}
I usually wait until something cracks. The good bits will get stripped and put into the parts bin. If I feed the bin well enough a new bike will grow.