According to Securing your wallet on bitcoin.it https://en.bitcoin.it/wiki/Securing_your_wallet#Securing_the_Bitcoin-QT_or_bitcoind_wallet by default there is only 100 keys in the key pool. You can manually specify a larger key pool with "-keypool" command line argument.

What this means is that after 100 transactions new keys are generated to replenish the old ones(by default).When this is done you need to have a backup of this new wallet as keys have changed. Your safest bet is to routinely back it up after creating new addresses or after sending a couple of times.

read over the securing your wallet section on the link as it will give a better explanation. Unless you regularly create new addresses or send you should be fine with backing up every few weeks/months.

Having too many backups won't hurt of course and be sure to test your backups on another machine to make sure the wallet.dat is still functioning correctly.