A vaccine capable of protecting against Toxoplasma gondii would have both beneficial medical and veterinary impacts. Successful vaccination of humans would not only reduce mortality and morbidity, but also reduce the financial burden of lifelong care required by those worst affected. A veterinary vaccine would have the dual advantages of increasing livestock productivity while reducing the public health risk associated with eating contaminated meat. Herein we review progress towards these goals using both large animal studies and the murine models of disease. Early approaches were largely empirical and used attenuated organisms, parasite extracts, or defined sub-units based upon the limited genomic data previously available. The recent elucidation of the T. gondii genome, understanding of T. gondii population structures, predicative algorithms for MHC binding peptides, facile manipulation of T. gondii taken together with a wealth of immunological knowledge should significantly promote new vaccine development.