Plant disease resistance is often determined by complementary pairs of resistance genes (from the plant) and avirulence genes (from the invading pathogen). This gene-for-gene interaction has generally been interpreted as a receptor-ligand model in which the avirulence protein binds to the corresponding resistance protein, which in turn initiates plant defense. Recent studies indicate that co-localization of avirulence and resistance proteins is essential for their function. However, there is also accumulating evidence that resistance proteins are not the primary receptor for the avirulence protein. We review advances in our understanding of gene-for-gene resistance and examine validity of the receptor-ligand model and other proposed models in the context of the most recent findings.