The field of neonatal immunology and calf vaccination is going through a revolution in veterinary medicine. The purpose of this article is to give an overview of basic neonatal immunology and principles of vaccination as they relate to beef and dairy calves. Opinions on when and what to vaccinate calves for vary widely among experts; therefore, this article focuses primarily on the documented literature. It is likely that vaccination approaches that might be effective or economic for one herd may not work for another.