Harvest mature leaves. When the leaves look mature enough to eat - they should resemble lettuce leaves you'd buy in the grocery store - you can break them off directly from the plants. After a few weeks, when the plant is mature, you'll want to cut the whole plant from the ground. If you leave it in it will eventually go bad.
Harvest leaves in the morning. They acquire a crispness overnight, and they'll retain it if you harvest early.
Lettuce starts to "bolt" in hot conditions toward the end of the growing season. It begins producing seeds and acquires a bitter taste. You can keep this from happening by pinching off the center of the plant. If a lettuce plant does end up bolting, go ahead and pull it up