Solid organ transplant recipients (SOTRs) have a 50 to 250 times greater risk of squamous cell carcinoma (SCC) than the general population and experience higher rates of invasive and metastatic disease. These greater risks are a product of the tumorigenic effects of their immunosuppressive medications. As the number of transplantations and the life expectancy of SOTRs increase, SCCs are becoming a major source of morbidity and mortality. To present a practical approach for busy practicing clinicians to the care of SOTRs who are developing SCCs. Topics include assessment and treatment of new and neglected SOTRs; the dermatologist's role with the transplantation team; and practical considerations in the choice of topical agents, systemic agents, and immunosuppressive therapy manipulation. An extensive literature search of the understanding of SCC pathophysiology and treatment in SOTRs was conducted. Presented here is a logical, concise guide to the care of SOTRs who are developing actinic keratoses and SCCs. Proper assessment of patients, understanding therapeutic alternatives and their application, and early institution of preventative and adjuvant therapies can help to decrease skin cancer-related morbidity and mortality in SOTRs. © 2012 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.