The easiest way in is through the front door.
It doesn't matter how well protected your network is, poor judgement and/or user error accounts for most malicious intrusions into your business environment. Not everyone is a computer expert, nor should they have to be. An errant 'click' here or a mis-typeed webpage there can lead to malware, spyware, and viruses establishing a foothold in your domain. Good quality and well managed anti-virus and anti-malware products are a must for all computers in your network. It is not enough to just install a program and hope for the best; it must be looked after and managed in order for it to do its job.