The Red Queen Hypothesis (RQH) explains how pathogens may maintain sexual reproduction in hosts. It assumes that parasites become specialized on common host genotypes, reducing their fitness. Such frequency-dependent selection favors sexual reproduction in host populations. Necessary conditions are that resistance and virulence are genotype specific so that host genotype frequencies respond to changes in pathogen genotype frequencies, and vice versa. Empirical evidence on the genetic basis of disease, variation in resistance and virulence, and patterns of infection in sexual and asexual plants support certain features of the hypothesis. However, gene-for-gene interactions are generally not consistent with the RQH because they do not result in cycling of gene frequencies, unlike a matching allele mechanism. A conclusion of whether the RQH can explain the maintenance of sexual reproduction cannot be reached at present. Nevertheless, the RQH theory has shed light on many aspects of plant/pathogen interactions important for reducing pathogen damage in agricultural systems.