I came across this article on Cisco’s site:

[1] http://www.cisco.com/warp/public/105/pmtud_ipfrag.html

It’s a great read, and covers a lot of information that will help you minimize fragmentation issues across your network.  It’s great for understanding when routers fragment packets and how to configure Path-MTU-Discovery.  It’s also helpful if you have GRE or IPsec tunnels in your network.

One thing that stands out is to remember that Path-MTU-Discovery relies heavily on certain ICMP messages.  Routers reply with “fragmentation needed and DF set” and you won’t hear about it if your firewall is blocking ICMP.