Cytomegalovirus (CMV) infection in immunocompromised host is an important cause of morbidity and mortality. The protective immunity against the virus is both humoral and cellular. Immunologic mechanisms in rejection as in the immune response against CMV infection are similar but there is difficult to separe as histologic and clinically independent events. At least eight different genes of CMV are homologous to human proteins related to the immune response. The potential role of these genes with homology to human genes can be at different levels. The relevance that immunodominant antigens have on the natural control of CMV infection, suggests that the future design of a vaccine directed to protecting from disease those susceptible to primary infection, in an immunocompromised state, should involve a combination of antigens that include pp65, IE1-exon 4 and gB as a recombinant proteins.