Has he flown before? Takeoff, landing, and everything in between -- turbulence, pressure-filled ears, prolonged sitting -- can sometimes be tough for a child to handle, even with you there. But it could still be okay if your child adapts well to new experiences.
Can he entertain himself? Don't assume the flight attendant or his seatmates will talk to your child at length, much less sit down to a game of Scrabble. To give him a test run, set him up with a few of his favorite handheld games, some books, and a few snacks, and see if he can play, read, and rest for the same amount of time it would take to get to Grandma's.
Does he respect authority? He'll have to listen to and take directions from the flight staff. It's good if he gets along with his teachers. But the real test is whether he'll do as his friend's mom says. If he tends to give her a hard time, he might do the same with the flight attendant.
Will he ask for help? Some kids are uncomfortable talking to grown-ups, but when traveling alone, your child must be able to speak up if he needs something.
If he's ready, prepare him for takeoff! Help him put together a travel care package -- a favorite book, portable CD player (to be used only when permitted), gum. Tell him what to expect on the flight, and go over rules of passenger courtesy -- get up only to use the restroom, don't disturb anyone, and call the flight attendant for emergencies only.