Medium-depth chemical peels in combination with focal cryotherapy (liquid nitrogen) can be a highly effective means of reversing photodamage and subclinical actinic damage while also minimizing actinic keratosis recurrence rates and reducing the risk of skin cancer development. This dual-therapy treatment has minimal downtime, produces little discomfort, and is cost-effective. Earlier laboratory research has demonstrated that trichloroacetic acid (TCA) peels can reduce cutaneous malignancy formation as well as suppressing the retention of p53-positive abnormal cells. Human studies with medium-depth TCA peels have found similar outcomes in photodamaged subjects—significant reduction in actinic keratoses as well as chemopreventive effects. Medium-depth peels produce a controlled cutaneous injury into and through the papillary dermis, which ultimately results in epidermal turnover and neocollagenesis. In the aesthetic sense, these changes translate into improvement in fine wrinkling, dyspigmentation, and texture. Tailoring the pre-conditioning and post-care regimen, modifying the peel concentration, and application times of liquid nitrogen can allow chemical peeling and cryotherapy to be safely used in the spectrum of skin types. A case presentation utilizing this multimodal field and focal therapy for photodamage and widespread actinic keratoses is outlined. Identification and management of possible complications are also reviewed.