Polyamines (PAs) are natural aliphatic amines involved in many physiological processes in almost all living organisms, including responses to abiotic stresses and microbial interactions. This review presents the profuse evidence that relates changes in polyamines levels during responses to biotic and abiotic stresses in model and cultivable species within Leguminosae, and examines their potential roles in the functioning of symbiotic interactions with nitrogen fixing bacteria and arbuscular mycorrhizae. The family Leguminosae constitutes an economically and ecologically key botanical group for humans, being also regarded as the most important protein source for livestock. The ability of legumes to establish symbiotic interactions with nitrogen fixing bacteria and arbuscular mycorrhizae fungi, gives to some legume species that are able to exploit their molecular machinery “pioneer” attributes, with better competition in nutrient-poor soils and higher adaptation to restricted environments. However, many legume crops may be affected by climate change-derived environmental stresses, whereby maintaining their yields safe from adverse environmental conditions is probably one of the biggest challenge facing modern agriculture. Therefore, the obtaining of vigorous genotypes with higher tolerance to abiotic and biotic stressors has turned an increasingly important biotechnological target. At this scenario, PAs can play an important role, and genetic manipulation of crop plants with genes encoding polyamine PA biosynthetic pathway enzymes is envisioned as a strategy to achieve plants with improved stress tolerance and symbiotic performance. As linking plant physiological behavior with "big data" available in "omics" is an essential step to improve our understanding of legumes responses to global change, we also examined integrative MultiOmics approaches available to decrypt the interface legumes-PAs-abiotic and biotic stress or interactions. These approaches are expected to accelerate the identification of stress tolerant phenotypes and the design of new biotechnological strategies to increase their yield and adaptation to marginal environments, making a better use of available plant genetic resources.