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New innovations have led to improvements in the safety and efficacy of vaccines, from live attenuated viruses to subunit vaccines, to RNA\u2010based vaccination for SARS\u2010CoV\u20102. Despite this progress, however, solid organ transplant (SOT) recipients on immunosuppression demonstrate an impaired vaccine response compared with healthy controls. This issue is important given the increased vulnerability to infection in immunocompromised patients, especially in the setting of the Coronavirus Disease 2019 (COVID\u201019) pandemic.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We reviewed the literature on key topics in vaccination with significant clinical impact on SOT patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Prior to COVID\u201019, a large amount of data has been published demonstrating impaired humoral and T\u2010cell responses to multiple vaccinations targeting influenza, hepatitis B, VZV, and Pneumococcus. Poor immunogenicity can be addressed through the use of adjuvants to boost the immune response, even in the setting of senescence related to age or immunosuppression. New vaccines provide hope for preventing infection due to hepatitis C and <jats:italic>Cytomegalovirus<\/jats:italic>, and to the emerging infection, monkeypox. The data on the impact of the COVID\u201019 vaccine in SOT patients is reviewed, with a focus on seroconversion, antibody titer, and antigen\u2010specific T cells. Factors associated with impaired response, including mycophenolate, are described.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The history of vaccination demonstrates how scientific breakthroughs can be applied to clinical challenges. New approaches using adjuvants, strategic antigen selection, and RNA\u2010based vaccines offer the potential to improve immune response in SOT recipients. 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