Over the past 50 years, the practice of vaccination has reached the important goal of reducing many of the diseases that afflicted humanity in past centuries. A better understanding of immunological mechanisms underlying the induction of immune protection and the advent of new technology led to improved vaccine preparations based on purified microbial antigens and new adjuvants able to boost both humoral and cellular immune responses. Despite these tremendous advances, much remains to be done. The emergence of new pathogens, the spread of strains resistant to antibiotics and the enormous increase in latent infections are urgently demanding more and more effective vaccines. Understanding the immunological mechanisms that mediate resistance against infections would certainly provide valuable information for the design of new candidate vaccines.