Actinic keratoses are unsightly and may be precancerous. Solitary or localized lesions respond adequately to many forms of treatment. However, widespread multiple actinic keratoses can best be treated with topical 5‐fluorouracil. The exact mode of action is not known, but we can presume it is related to the clearly established effect of this drug upon RNA and DNA synthesis. This treatment is almost ideal, since it usually destroys the keratoses selectively, without significant alteration in normal skin. A 1 or 2 percent solution is made by diluting the 10 ml ampule with propylene glycol. This liquid is applied two times daily to the involved areas for a 2–4 week period. Lesions on the face and neck respond more quickly than those of the hands and arms. A brisk, painful, inflammatory reaction at the site of the keratoses is anticipated and used as an indicator of the end point of treatment. Once treatment is discontinued, the erythema usually subsides in 2 weeks and the skin becomes smooth and free of keratoses. Not all keratoses respond, and untoward reactions such as phototoxicity, irritation of the mucous membranes, contact sensitivity, and alteration of pigmentation can occur. Although resolution of the keratoses persists for years, should they return reapplication is usually effective again.