Host–microbe interactions in the rhizosphere influence numerous processes that determine plant productivity and health. The rhizo-microbiome influences functions ranging from protection of the plant from pathogen attack to enhanced nutrient availability and uptake. This chapter examines the use of ‘omics’ technologies to address key issues in plant–microbe interactions including the effects of the rhizosphere microbiome in determining plant health and production when interacting with their environment. After examining the contribution of the microbiome in directing plant responses to their environment, the chapter provides two case studies focusing on manipulation of the rhizosphere microbiome to optimize crop production on orchard replant sites. Finally, the chapter looks ahead to future research trends in this area and provides detailed guidance on further reading.