The potent systemic immunosuppression therapy necessary to sustain a life-saving solid organ transplant is associated with an increased incidence of various infections including human papillomavirus infection and skin cancers in organ transplant recipients. Imiquimod, a topical agent that functions through local induction of a specific anti-viral or anti-tumor immune response, appears to be a promising therapeutic option that could potentially counteract in situ the effects of systemic immunosupression in this vulnerable group. Up-to-date studies using this local immune-response modifier in transplanted patients have yielded reassuring and encouraging results regarding its safety and efficacy in this population. However, in order to establish the use of imiquimod as a standard treatment option for organ transplant recipients, additional research and clinical trials are required.