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Rhizosphere and plant-associated microorganisms have been intensely studied for their beneficial effects on plant growth and health. These mainly include nitrogen-fixing bacteria (NFB) and plant-growth promoting rhizobacteria (PGPR). This beneficial fraction is involved in major functions such as plant nutrition and plant resistance to biotic and abiotic stresses, which include water deficiency and heavy-metal contamination. Consequently, crop yield emerges as the net result of the interactions between the plant genome and its associated microbiome. Here, we provide a review covering recent studies on PGP rhizobia as effective inoculants for agricultural practices in harsh soil, and we propose models for inoculant combinations and genomic manipulation strategies to improve crop yield.