make sure the CPU and motherboard are compatible (duh!). also, do a little research beforehand and try to buy a MB that hasn't outlived its time yet, meaning a CPU upgrade in 2-3 years will be viable (also read up on its overclocking capabilities). make sure the MB has enough slots (for two videocards for example, if you're into that kind of stuff). also, my personal preference - a MB with an integrated videocard, just in case. you might want to keep using your RAM with it, so check if the MB supports it.
make sure your PSU can deal with new wattage (if you're not buying a new unit).
I have built a number of PCs, nothing too complicated. just read a bunch of reviews and pick a motherboard that suits your needs, then go from there. the secret is in the maintenance