Successful treatment of actinic keratosis (AK) requires an understanding of available treatments and matching those treatments with each patient's disease severity, lifestyle, insurance coverage, and primary reason for the physician visit. Cryotherapy and other destructive strategies are optimal for hypertrophic and clearly delineated lesions, but they may not address subclinical lesions and are associated with risk of scarring, infection, and pigmentary changes. Topical therapies such as the fluorouracil creams are appropriate for treating large regions of affected skin but are associated with application-site irritation. A combination of destructive and topical approaches may benefit patients with multiple lesion pathologies.