Solid organ transplant recipients (SOTRs) are at high risk for infections including SARS-CoV-2, primarily due to use of immunosuppressive therapies that prevent organ rejection. Furthermore, these immunosuppressants are typically associated with suboptimal responses to vaccination. While COVID-19 vaccines have reduced the risk of COVID-19–related morbidity and mortality in SOTRs, breakthrough infection rates and death remain higher in this population compared with immunocompetent individuals. Approaches to enhancing response in SOTRs, such as through administration of additional doses and heterologous vaccination, have resulted in increased seroresponse and antibody levels. In this article, safety and immunogenicity of mRNA COVID-19 vaccines in SOTRs are explored by dose. Key considerations for clinical practice and the current vaccine recommendations for SOTRs are discussed within the context of the dynamic COVID-19 vaccination guideline landscape. A thorough understanding of these topics is essential for determining public health and vaccination strategies to help protect immunocompromised populations, including SOTRs.