If this happened, it means what were thought of as "cold wallets" were not implemented properly. When handling millions of dollars of coins, as Cryptsy was, a deep cold wallet [1] should be used. Take an offline computer and an offline printer. Generate a bunch of (optionally multisig) addresses. Print the private keys. Copy the addresses to your server that processes transactions. Lock away the private keys (optionally in multiple places). Never connect the offline computer or printer to the internet. Send every X bitcoins to a new address from the cold wallet.
This takes a few hours and a few hundred bucks to implement. It requires human intervention to access the cold wallet (to replenish the internet-facing "hot" wallet), but that is what you want! It is a whole lot easier to manually move coins once a week than it is to check for bugs and backdoors in your whole stack. Worst case, customers suffer a delay in withdrawals and a hack causes you to lose X bitcoins.
Edit: Of course, it could also be an inside job. An "exit scam." Moving coins to a new address and then not spending them is pretty hard to get caught doing.