Advances in molecular biology, cell biology, and several other areas of science have changed the way we understand the mechanisms in which microbial pathogens interact with their hosts. This trend is set to continue with the advent of microbial genome sequencing, in vivo gene expression analysis, and other related techniques. The availability of these techniques and advances in other areas such as protein expression and crystallography has allowed the understanding of host pathogen interaction at the molecular and even atomic level. However, despite these powerful approaches the basic concept advanced many years ago by Smith that pathogenicity or virulence is a multifactorial property that consists of five basic steps is still valid today.1 The molecular basis of virulence can still be considered under these five headings: (1) attachment to the host (via mucous membranes); (2) entry into the host (usually); (3) multiplication within the host; (4) Interference with host defence systems; (5) damage to the host.

These five stages are not mutually exclusive. The factors produced by pathogens that mediate these steps are termed the determinants of microbial pathogenicity. The molecular basis of these steps will be considered and specific examples will be given to demonstrate the basic principles. Finally it should be emphasised that expression of determinants of pathogenicity is usually regulated and systems exist for environmental sensing and quorum sensing to allow appropriate expression of virulence factors.