Crop production is significantly dwindled by a plenitude of pathogens that deprive the host plants of nutrients, alter their physiological processes, and ultimately reduce yield. In order to combat biotic stress and enhance their survival, plants have evolved innate immunity which recognizes the presence of pathogens and stimulates defense responses via PAMP-triggered immunity and effector-triggered immunity. The successful activation of plant immune responses and subsequent pathogen defense is governed by an interplay of various phytohormones and signaling molecules of which the role of salicylic acid, jasmonic acid, and ethylene, among others, is well established. In addition, a growing body of evidence also suggests a key role of polyamines (PAs) in the regulation of plant immune responses. Based on the literature evidence, it can be concluded that plants capable of synthesizing PAs during the initial stages of pathogen invasion exhibit resistance, and the PAs so produced are later catabolized to synthesize other signaling molecules such as H2O2 which is required to initiate hypersensitive response induced cell death. This review encapsulates the metabolism of PAs and their role in the amelioration of biotic stresses induced by various pests and pathogens. Further, the crosstalk of PAs with different signaling molecules in modulating the defense system in host plants in response to biotic stress is also presented.