In the present review, we concentrated on primary signaling and regulatory events in plant cells that are rapidly evoked in response to extracellular polyamines in vivo and induce cellular and biochemical responses. Downstream pathways that allow polyamines to regulate plant growth, development, and stress tolerance are analyzed. The results of the recent studies on polyamine metabolism and its regulatory mechanisms are also discussed. Taken together, the data suggest that endogenously and exogenously regulated polyamines by activating ion transport, calcium dynamics, lipid, protein kinase, protein conjugation, and nucleic acid regulation mechanisms modulate downstream transcriptomic, proteomic, metabolomic, and hormonal pathways affecting growth, development, and stress tolerance.