A comfortable seat can be hard to come by. The following are three common issues related to getting comfortable on a seat. The first is the more daunting one, and is addressed more fully elsewhere in this site.
Sitting Bone Pain
Probably the most challenging sources of seat discomfort to conquer is painful "sitting bones." As shown in the diagrams, these are actually bones, called the ischium, which are part of our pelvic structure. These bones carry a the bulk of a rider's weight when sitting on a seat. Some seats are so uncomfortable that the sitting bones can start hurting within 30 minutes after the start of a ride. To get an idea of how much the sitting bones, or ischium, are involved in sitting and riding, archeologists exploring ancient Chinese grave sites supposedly can determine ages of cavalry soldiers based on how much their pelvic bones are worn.
Much of the sections on this site about modifying your seat deal with tackling this problem.
The tailbone is actually the final segment of the vertebral column (see the picture below). It is attached to the sacrum by a fibrocartilaginous joint (the sacrococcygeal joint) that allows it to move a bit. Because this joint is flexible, riding on a bike can cause it to move; and if the joint becomes irritated, this can be one of the causes of pain. If you've ever experienced tailbone (coccyx) pain, you know how debilitating it can be. In some cases, it's almost impossible to sit for more than a brief period of time without serious pain. More chronic tailbone pain is called coccydynia (check out this site to get more info on this condition and treatments). It's virtually impossible to have much fun riding with coccydynia. Causes of tailbone pain can be injuries, too much sitting, and even childbirth. Typically, it takes care of itself. The worst case scenarios result in the surgical removal of the tailbone (coccygectomy).
Notice that the picture below shows a more upright cruiser or sport-touring riding position. This position typically causes more pressure to be placed on the coccyx. The feet are forward, thus not supporting the downward pressure on the back. The back is also relatively straight, which places more bending pressure on the coccyx. For most riders, this isn't a problem. However, for those with tailbone or coccyx pain, this situation can be agony. Other than medical treatment for this condition, there are some things that you can do to your seat to alleviate this pain. Check out this page for one solution.
Rash is a skin irritation caused by perspiration that damages cells on the surface of the skin, and traps the sweat beneath the skin. As sweat continues to build up it causes bumps on the skin. When these bumps burst, sweat escapes into adjacent tissue, causing a stinging, uncomfortable sensation. For obvious reasons, hot, humid weather is often a culprit of butt rash. A sweaty, non-breathing riding suit or leaky rainsuit can also cause rash. Some seat pads that increase air circulation, moisture-absorbing undershorts, and breathable riding pants can all help prevent rash.
Chafing occurs as friction against the skin causes irritation and soreness. Chafing on your buttocks while riding usually occurs when your skin presses against seams in your underwear or seat for a prolonged period. It can also happen when your thighs rub the edge of the seat that's not shaped well for the rider. A few clothing brands offer underwear (e.g., Jockey, Aerostich) that eliminates the seam on your buttocks. Some riders wear bicycle shorts to eliminate the seams, and for the extra cushion and moisture absorbtion of the padding in the crotch. If the stock seat (versus cloting) has seams that cause irritation, a new seat, seat cover, or a seat pad may be the only fix.