The production of disease requires the expression of a series of important genes that allows the pathogen to adapt to hostile environment in the host. The expression of these genes contributes to the virulence of pathogens and such genes encode products frequently termed “virulence factors.” In traditional sense, virulence factors are thought to include toxins attachment factors and hydrolytic enzymes that contribute directly to disease. For example, cell surface structures have been characterized in bacteria that permit both attachment and entry into epithelial cells and pathogenic bacteria may use any of a number of proteinaceous (protein-cleaving) virulence factors to infect the host through the respiratory, gastrointestinal, or genitourinary tract. Likewise, group A Streptococci use lipoteichoic acid (LTA) and/or M proteins to facilitate attachment and infection. The inhibition of virulence factors(s) would not kill bacteria, but rather would stop the initial colonization and subsequent infection. The chapter explains some examples of the successful use of cell surface or virulence antigens as targets for the intervention through vaccine development and virulence antigens under study as potential vaccines. Such a strategy has also been applied to the anti-viral arena, but has not been successfully applied to the area of anti-fungals.