You're sitting too close to your monitor.
Constantly focusing on close objects without a break can strain your eyes. Make sure you're sitting at the proper distance from your monitor - about arm's length away for 17" monitors. See Monitor Setup and Usage, or the article Reducing Eyestrain.
You've been working too long without resting your eyes.
Your eyes are muscles, too, and need regular breaks to avoid feeling weary from overuse. Follow the 20/20/20 rule - every 20 minutes, look at least 20 feet away for 20 seconds. See Monitor Setup and Usage.
You're not blinking often enough.
Although blinking is a reflex, we tend to blink less often when looking at a computer than when reading or performing other tasks. This causes our eyes to become dry, uncomfortable, and even blurred. Remember to blink, or even consider artificial tears.
You wear glasses or contacts, and the prescription is out of date.
Your eyes may be working harder than you think if your prescription doesn't offer the right correction. Make sure that you've had a recent eye exam and that your prescription is up to date.
There's inadequate lighting or possibly too much lighting.
Inadequate lighting can force your eyes to "work overtime" to read from the screen (or force you to move in closer so that it's visible). Too much lighting can cause glare or reflection. Both may lead to eyestrain and headaches. For a complete discussion of lighting issues, see Lighting Setup and Usage or see Monitor Setup and Usage.
There's poor contrast on your screen, or the refresh rate is too low.
Working with inadequate contrast settings can force your eyes to work harder to differentiate characters. A refresh rate that's too can cause both eyestrain and headaches. To learn how to properly adjust both, see Lighting Setup and Usage, see Monitor Setup and Usage, or the article Reducing Eyestrain.