The molecular research into two types of beneficial plant-microbe symbioses is reviewed: nutritional (with N(2)-fixing bacteria or mycorrhizal fungi) and defensive (with endo- and epiphytic microbes suppressing pathogens and phytophagans). These symbioses are based on the signaling interactions that result in the development of novel tissue/cellular structures and of extended metabolic capacities in the partners, which greatly improve the adaptive potential of plants due to a decrease in their sensitivity to biotic and abiotic stresses. The molecular, genetic and ecological knowledge on plant-microbe interactions provides a strategy for the organization of sustainable crop production based on substituting the agrochemicals (mineral fertilizers, pesticides) by microbial inoculants. An improvement of plant-microbe symbioses should involve the coordinated modifications in the partners' genotypes resulting in highly complementary combinations. These modifications should be based on the broad utilization of genetic resources from natural symbiotic systems aimed at: (i) increased competitiveness of the introduced (effective) with respect to local (ineffective) microbial strains, and (ii) overcoming the limiting steps in the metabolic machineries of the symbiotic systems.