Plants face continuous attacks from a broad range of pathogens and have evolved effective defence mechanisms that are initiated upon pathogen attack. Invading oomycete pathogens secrete effectors, molecules that manipulate host cell defence and thereby enable colonization. However, plant species evolved resistance (R) genes to most specialized pathogen species. The R proteins can detect effectors, termed avirulence (AVR) proteins, and thus confer immunity to pathogens. Effectors and their interacting genes in the plant play a central role in the co-evolution of pathogens with their hosts. In this review, we discuss the role that effectors play in the pathogenesis and lifestyles of oomycetes. Particularly intriguing features emerge for (hemi-)biotrophic oomycetes, which establish an intimate contact with the host by forming haustoria. At this interface, effectors with an RXLR motif are translocated into the cytoplasm, where they reprogramme the host towards susceptibility. Such interactions between effectors and host targets are highly specific and are considered a result of tight co-evolution. In addition, we elaborate on the Phytophthora infestans-Solanum pathosystem, from which various R and Avr genes were cloned recently. We discuss a rationale for exploiting molecular insights into R-Avr interactions for developing more durable resistance strategies to control late blight in agriculture.