Much of a dermatologist's career will be spent treating actinic keratoses (AKs). Cryotherapy is the mainstay treatment of AK, and for most clinicians it is the de facto treatment of individual lesions. Topical therapies are highly utilized alternatives to cryotherapy with numerous agents now approved by the US Food and Drug Administration. No treatment algorithm currently exists for first-line or second-line therapies due to a lack of comparative studies, which makes it challenging to identify which treatment is best for an individual patient. This article reviews the most relevant comparative studies with a focus on treatment efficacy. The author also presents her approach to the use of these medications.