I have a PO Box - it's just a locked box at the post office that your mail gets delivered to, keeps it dry and from getting stolen. No different than if you live in an apartment building.
I live rural just like Michelle pointed out, The mail runs only to the main road, I live a mile down a dirt road in the woods so technically off the mail route and I can't see the road or the boxes from my house. I've had the same PO Box address through three moves in over twenty years, when we first moved to this town and lived in one of the hubs Grandparents rentals, when we moved to our own place, and when we built our home. No lost mail in transitions because the address never changed.
UPS and FedEx both now have mail options as well, mail innovations or something like that.
In answer, I can't think of a single reason why I wouldn't mail to a PO Box :)