Binding of microbial cell surface adhesins to host receptor molecules is a critical early step in microbial infection and pathogenesis. Anti-adhesive strategies aimed at blocking this interaction offer an attractive means of preventing infection at an early stage. The strategy should reduce the likelihood of resistant strains of microorganisms emerging, since those that do not bind will not be subjected to sustained selective pressure, as may occur with antibiotic therapy. Three classes of adhesion-blocking agent have been investigated, namely anti-adhesin antibodies, adhesin analogues and receptor analogues. The effectiveness of a number of these adhesion-blocking compounds has been demonstrated in human and animal models of infection. Direct application to the tooth surface of anti-adhesin monoclonal antibody, or a synthetic peptide adhesion epitope, prevented infection with the oral pathogen, Streptococcus mutans in humans. Intranasal administration of a soluble receptor analogue significantly reduced virus production and symptoms following experimental infection with rhinovirus. Similarly, all three types of anti-adhesion agent protected against a variety of infections at other mucosal surfaces in animal models. A common finding from these studies is the long duration of protection, which cannot be due to persistence of the anti-adhesion agent, but may be the result of competitive exclusion by members of the normal flora at specific mucosal surfaces. Development of these novel antimicrobial agents is particularly timely in view of the increasing concern over the spread of antibiotic resistance.