The new target for the treatment of actinic keratosis (AK) is the detection and clearance of clinical and subclinical lesions across an entire sun-exposed field. This is because patients with AK have field cancerization as ultraviolet light affects the entire sun-exposed area and because it is not possible to predict which AK lesions will progress into invasive squamous cell carcinoma. To fully assess the effectiveness of field-directed therapies against the full burden of AK, a new efficacy concept has been developed which is based on the reduction in lesions from Lmax, or the maximum lesion count during treatment. This new parameter enables the efficacy of a field-directed therapy against both clinical and subclinical lesions to be assessed. Imiquimod 3.75% is a novel field-directed therapy which uniquely can detect and clear both clinical and subclinical lesions across a large sun-exposed field such as the full face or balding scalp, and so far is the only AK treatment to have had its efficacy assessed with the Lmax concept. The detection of subclinical lesions is evidenced by an increase in lesion count during each of the 2-week treatment cycles, which are separated by a 2-week treatment-free interval. The median percentage reduction in lesions from Lmax with imiquimod 3.75% is 92%, and the effective clearance of both clinical and subclinical lesions leads to sustained lesion clearance for at least 1 year. Imiquimod 3.75% has an acceptable tolerability profile. Rest periods from treatment may be taken if required to manage local skin reactions, with no loss in efficacy. In conclusion, Lmax and imiquimod 3.75% together set the new standard in the management of patients with AK.