The first decade of the millennium should mark the beginning of a new era in vaccine development, reaping the rewards of advances in genome characterization, antigen identification, understanding the molecular bases of protective immune responses, and adjuvant design and development. Advances in all of these areas have culminated in vaccine candidates entering clinical testing. These include vaccines against two of humankind's oldest and deadliest diseases, tuberculosis and malaria. Several vaccine candidates for each of these diseases will be tested in humans during the next few years. A candidate vaccine for leishmaniasis, an infection that has taught us much about T-cell regulation of protection and disease in animal models, has been developed and is now in the clinic. There are indications both in animal models and in patients that vaccines may be used not only to protect but also to treat leishmania infections.