Many vaccines existing today provide strong protection against a wide variety of infectious organisms, and these consist of either live attenuated or inactivated microorganisms. Most of these vaccines were developed empirically and there has not been a clear understanding of the immunological principles that contribute to this success. Recent advances in systems biology are being applied to the study of vaccines in order to determine which immunological parameters are the best predictors of success. New approaches to vaccine development include the identification of peptide epitopes and the manipulation of the immune response to generate the most appropriate response. Vaccines are being developed to prevent and/or treat such conditions as cancer and autoimmunity in addition to infectious diseases. Vaccines targeting this diverse group of diseases may need to elicit very different types of immune responses. Recent advances in our understanding of the functions of dendritic cells (DC) and cytokines in orchestrating qualitatively different immune responses has allowed the design of vaccines that can elicit immune responses appropriate for cancer, autoimmunity or infectious organisms. This review will focus on recent advances in the ways DC and cytokines can be used to develop the most appropriate and effective vaccines.