Bacillus anthracis is the causative agent of anthrax, a disease that plagues both humans and various animal species. Effective vaccines are available, but those approved for human use are crude culture supernatants that require multiple injections and a yearly boost. Many experts agree that it is now time for the next generation of human vaccines against anthrax. Accordingly, this review will succinctly focus upon: pathogenesis of B. anthracis, with particular emphasis upon the immune system; the pertinent biophysical nature of protective antigen, which includes how the protein toxin component affords protection as a vaccine target; alternative methods for improving protective antigen as an immunogen; and additional B. anthracis antigens that might further sustain protective titers in humans. In addition to a better understanding of the disease process elicited by B. anthracis, which will logically lead to better vaccines (and therapeutics), there also needs to be the same level of open-mindedness applied to the politics of anthrax.