The sciences of vaccinology and of immunology were created just two centuries ago by Jenner's scientific studies of prevention of smallpox through inoculation with cowpox virus. This rudimentary beginning was expanded greatly by the giants of late 19th and early twentieth centuries biomedical sciences. The period from 1930 to 1950 was a transitional era with the introduction of chick embryos and minced tissues for propagating viruses and Rickettsiae in vitro for vaccines. Modern era vaccinology began about 1950 as a continuum following notable advances made during the 1940s and World War II. Its pursuit has been based largely on breakthroughs in cell culture, bacterial polysaccharide chemistry, molecular biology and immunology, which have yielded many live and killed viral and bacterial vaccines plus the recombinant-expressed hepatitis B vaccine. The present paper was presented as a lecture given¹ on August 30, 1999 and recounts, by invitation, more than five-and-half decades of vaccine research from the venue of personal experience and attainment by the author. The paper is intentionally brief and truncated with focus only on highlights and limited referencing. Detailed recounting and referencing are given elsewhere in text references [Hilleman MR. Six decades of vaccine development — a personal history. Nat. Med. 1998;4 (Vaccine Suppl.): 507–14] and [Hilleman MR. Personal historical chronicle of six decades of basic and applied research in virology, immunology and vaccinology. Immunol. Rev. (in press)]. This narration will have achieved its purpose if it provides a background of understanding and guidelines that will assist others who seek to engage in creation of new vaccines.