Haemophilus somnus, Actinobacillus pleuropneumoniae and Pasteurella haemolytica are economically important bacteria with pathogenic characteristics that require us to look further than killed, whole cell bacterins for induction of a protective immune response. A strong immune response is not synonymous with protection and the extreme specificity of the immune response works to our disadvantage when broad protection is needed. Detection of animals that are susceptible or immune to infection is important for the purpose of diagnosis and epidemiological study. However serum antibody levels are rarely indicative of protection unless it is known that the antibody of a particular isotype must be directed against a specific epitope for protection to occur. Parenteral vaccination with killed, whole cells of H. somnus, A. pleuropneumoniae or P. haemolytica produces, respectively, adequate protection, partial protection and increased disease. The reasons for these differences and methods of improving protection, based on an understanding of virulence determinants, are discussed.