Your wrists aren't in a neutral position - they're bent up, down, or sideways.
Wrists should be kept straight - in line with the rest of the arms. People with broad chests may prefer a split design keyboard, as their elbows are already pushed slightly outward, naturally angling their wrists toward each other. Conversely, thinner people may find a traditional "straight" keyboard more comfortable. See Keyboard Overview and Accessories or Keyboard Setup and Usage.
Your keyboard feet are extended, tilting your keyboard up.
Your keyboard should have a neutral or slightly negative tilt. See Keyboard Setup and Usage.
Your mouse isn't positioned correctly - it may be too far away.
Your mouse should be at approximately the same level as your keyboard, and positioned close to your keyboard so that you don't have to reach. See Mouse Setup and Usage.
Your keyboard is placed too high or too low.
Your keyboard should be in a position that allows your elbows to keep an open angle (i.e. your forearms bent no higher than parallel to the floor, with your elbows close to your sides). See Keyboard Setup and Usage.
The edge of your desk or a hard wrist rest is putting pressure on the palm side of your wrist.
Consider a wrist wrest and/or check the height of your keyboard. See Keyboard Setup and Usage.
You're striking the keyboard too hard.
Try to use the minimum amount of force necessary to depress the keys. Hitting them too hard can lead to finger, hand and wrist pain. See Keyboard Setup and Usage.
Your mouse isn't the right size, or you're a left-handed person using a right-hand mouse.
Most people don't realize that mice can come in different sizes and orientations. Find one that fits comfortably in your hand. See Mouse Overview and Accessories, or Mouse Setup and Usage.
Your elbows may be too far from your body.
Remember that your elbows should rest comfortably close to your body. If they're too far to the side, this can force you to bend your wrists - leading to hand and wrist pain.
You're typing or keying too long without a break.
Overuse can lead to pain - this frequently occurs after you've been keying too fast or for too long without a break. Make sure to take frequent "mini-breaks - these can be as short as 15-30 seconds. Also, consider stretching during this period. See Stretches and Exercises.
Your keyboard isn't directly in front of you.
If your keyboard is off to the side, you may be angling your wrists to type. Position the keyboard directly in front of you. See Keyboard Setup and Usage.
You may need an ergonomic pen.
If you grip a pen or pencil for most of the day, try using one with a wider base or consider buying a rubber grip for your pen. This allows you to grasp the pen with less pressure, and should feel more comfortable.