This chapter provides an overview of the present knowledge relating to the various parameters of the immune system, immunotoxicology, and properties of vaccine adjuvants. Many systems, organs, and cells play a role in the immune response, which generally starts with the introduction of these foreign substances, which are defined as antigens, into the organism, and continues with many interrelated biological reactions. Studies on animals and humans have shown that the immune system is a potential target for a variety of vaccine adjuvants which increase the immunogenicity of an antigen but are not antibodies or immunogenic. To ensure the safe administration of vaccine adjuvants to humans, vaccines are evaluated in various nonclinical toxicity studies. In toxicology studies of adjuvants, acute dose toxicity, and repeated dose toxicities are primarily analyzed. This chapter summarizes the requirements for the nonclinical testing of vaccine adjuvants needed in support of all phases of human clinical trials.