Acne vulgaris is among the most common skin disorders afflicting adolescents worldwide, and though well-established guidelines of care exist for acne management, these guidelines do not uniformly consider or address the unique psychosocial and medical needs of transgender and gender diverse (TGD) youth. Part 2 of this two-part review provides guidance on a stepwise approach to the medical treatment of acne in TGD youth, with an emphasis on safety, efficacy, and the delivery of medical care in a culturally humble, thoughtful, and gender-affirming manner., (© 2022 Wiley Periodicals LLC.)