Cham-yes? or Cham-no? About half of the people I ride with wear a chamois, and the other half tend to avoid them. While some people have adapted and evolved to the point of rarely or never wearing one, others won't go on a spin around the neighborhood without some padding between their nether regions and their seat.
Speaking of seats, that part of the equation becomes even more important if you're thinking of leaving the padded undergarments at home. A good saddle can be the difference between a comfortable ride and spending the next few days walking around like a bowlegged cowboy. There's also something to be said about choosing high-quality underwear that's free of uncomfortable seams if you're going to head down the no-chamois route. On the flip side, keep in mind that padded cycling shorts are designed to be worn without underwear underneath - that knowledge isn't as common as you may think.
What is it for you?