The use of protein or DNA in vaccination process rather than living or attenuated microorganism, aims at the increase of the vaccines safety. However, in these cases, the use of adjuvant is frequently required to improve their immunogenicity. In this study, we show the importance of the adjuvant in a vaccine formulation. Vaccines for tuberculosis provide an instructive example, based on the mycobacterial 65 kDa heat shock protein (hsp65). The same antigen can elicit completely different patterns of immune response depending on how it is administered. Thus, the same antigen might or not protect mice from challenge with Mycobacterium tuberculosis, depending on the formulation. These data suggest that, despite the name, the adjuvant plays a fundamental role on the vaccination process.