Choosing a motherboard is the most interesting part of any building project. The reason it is so interesting is because there are hundreds of motherboards to choose from and each has its own advantages and disadvantages.

One easy way to think about motherboards is to break them up into a few categories. For example:

Cheap motherboards: Generally in the $50 range, these are motherboards for older CPUs. They are great for building inexpensive machines.
Middle-of-the-road motherboards: Ranging in price from $50 to $100, these are one step up from the cheap motherboards. In many cases you can find motherboard and CPU combos in this price range, which is another great way to build a cheap machine or an inexpensive home/office computer.

A middle-of-the-road motherboard
High-end motherboards: If you are building a powerful gaming machine or video workstation, these motherboards give you the speed you need. They range in price from $100 to $200. They handle the latest CPU chips at their highest speeds.
Extreme motherboards: Falling into the over-$200 range, these motherboards have special features that boost the price. For example, they might have multiple CPU sockets, extra memory slots or special cooling features.

You need to decide whether you are building a "cheap machine," a "high-end machine" or a "tricked-out super machine" and then choose your motherboard accordingly. Here are some other decisions that help narrow down your motherboard choices:

Image courtesy Intel Corporation

Do you want to use an Intel or an AMD processor? Making this choice will cut the number of motherboards in half. AMD chips are often cheaper, but lots of people are die-hard Intel fans.
What size motherboard do you want to use? If you are trying to build a smaller computer, you may want to look at micro ATX cases. That means you will need to buy a micro ATX motherboard. Otherwise you can use a normal ATX motherboard and case. (There are also smaller motherboard form factors like mini-ITX and even nano-ITX if you want to go really small.)
How many USB ports do you want? If you want several, make sure the motherboard can handle it.
Do you need FireWire? It's nice if the motherboard handles it (although it is also possible to add a card).
Do you want an AGP or PCI Express graphics card? Or do you want to use a graphics card on the motherboard to keep the price and size down? If you want to go the cheapest route, make sure the motherboard includes a video card on-board (easiest way to tell is to see if there is a DVI or VGA connector on the motherboard). PCI Express is the latest/greatest thing, but if you want to re-use an AGP card you already own, that might be a reason to go with AGP.
Do you want to use PATA (aka IDE) or SATA hard disks? SATA is the latest thing, and the cables are much smaller.
What pin configuration are you using for the CPU? If you want to use the latest CPUs, make sure that your motherboard will accept them.
Do you want to try things like dual video cards or special high-speed RAM configurations? If so, make sure the motherboard supports it.

If you don't care about any of this stuff (or if it all sounds like gibberish to you), then you're probably interested in building a cheap machine. In that case, find an inexpensive motherboard/CPU combo kit and don't worry about all of these details.