The hardest security threat to deal with is the insider threat. Most (by far!) security breaches come from insiders. As E. Cole points out detection and the reaction to this detection will improve your security a great deal, but (besides detection) how can you deal with this insider threat?
Well... there are certain things you can do. First divide responsibilities between different employees. Make sure that every (critical) business process there are multiple employees involved. This way detection of a security breach is easier and the impact of such a breach will be smaller.
The next thing would be to implement the principle of least privilege. Only allow employees to see what they need to see. This way a security breach will be less likely and the impact will be contained. The other benefit of this principle is traceability: you know who did what and where.
The last thing you can do is getting your physical access policy right and train your employees on security matters. Make sure you know who is inside of your building and make sure that if someone is inside of your building this person doesn't have full access. And train you employees on the matter of security. Make sure they know all the policies.
This won't guarantee full protection against insiders, but this will help you in detecting and containing security problems.