Resistance genes against Phytophthora infestans (Rpi genes), the most important potato pathogen, are still highly valued in the breeding of Solanum spp. for enhanced resistance. The Rpi genes hitherto explored are localized most often in clusters, which are similar between the diverse Solanum genomes. Their distribution is not independent of late maturity traits. This review provides a summary of the most recent important revelations on the genomic position and cloning of Rpi genes, and the structure, associations, mode of action and activity spectrum of Rpi and corresponding avirulence (Avr) proteins. Practical implications for research into and application of Rpi genes are deduced and combined with an outlook on approaches to address remaining issues and interesting questions. It is evident that the potential of Rpi genes has not been exploited fully.