The use of cytokines in the administration of vaccines has a unique value in obtaining the appropriate immune response and in ensuring a protective outcome. Earlier studies indicating that cytokines can influence the generation of a particular antibody isotype may represent an oversimplification of a more complex problem. Several studies discussed in this review show that the effect of a given cytokine on the immune response depends on whether one examines the antigen-specific response or the polyclonal response (i.e., total serum immunoglobulins). Further, a balanced regulation of immune responsiveness is important in maintaining homeostasis of the immune system. Consequently, for any vaccine that uses cytokines to boost the response, due consideration must be given to these important variables.