A blister is a small pocket of body fluid (lymph, serum, plasma, blood, or pus) within the upper layers of the skin, usually caused by forceful rubbing (friction), burning, freezing, chemical exposure or infection. Most blisters are filled with a clear fluid, either serum or plasma. However, blisters can be filled with blood (known as "blood blisters") or with pus (for instance, if they become infected).

Smaller blisters are called blebs. The word "blister" entered English in the 14th century. It came from the Middle Dutch bluyster and was a modification of the Old French blostre, which meant a leprous nodule—a rise in the skin due to leprosy.

In dermatology, the words vesicle and bulla refer to blisters of smaller or greater size, respectively.

Some sources recommend not to pop a blister. If popped, bacteria can enter. Excess skin should not necessarily be removed as the top layer protects the soft tissue underneath. However, some sources also recommend that if a blister is too big, it should indeed be popped.

A blister may form when the skin has been damaged by friction or rubbing, heat, cold or chemical exposure. Fluid collects between the upper layers of skin (the epidermis) and the layers below (the dermis). This fluid cushions the tissue underneath, protecting it from further damage and allowing it to heal.

Intense rubbing can cause a blister, as can any friction on the skin if continued long enough. This kind of blister is most common after walking long distances or by wearing old or poorly fitting shoes. Blisters are most common on the hands and feet, as these extremities are susceptible while walking, running, or performing repetitive motions, such as joystick manipulation whilst playing certain video games, certain sports (e.g., baseball pitching), digging with a shovel, playing guitar or bass, etc. Blisters form more easily on damp skin than on dry or soaked skin, and are more common in warm conditions. Less-aggressive rubbing over long periods of time may cause calluses to form rather than a blister. Both blisters and calluses can lead to more serious complications, such as foot ulceration and infection, particularly when sensation or circulation is impaired, as in the case of diabetes, neuropathy or peripheral artery disease (PAD).

This type of blistering is one of the tools used to determine the degree of burns sustained. First and second degree burns may result in blistered skin; however, it is characteristic of second degree burns to blister immediately, whereas first degree burns can have blisters after a couple of days. Sunburn can also result in blisters.

Blisters can also form on the hands and feet as a result of tissue damage incurred by frostbite.