Plant genomes encode over thousands of small peptides, whose functions remain mostly enigmatic. Nevertheless, some secreted peptides have been implicated to be important players in regulating diverse plant physiological processes, including cell growth, development, reproduction, immunity, and abiotic stress adaptations. Plant small peptides with immunomodulatory functions are also known as phytocytokines and can function as short- and long-distance defense signaling molecules. The phytocytokines can amply the immune responses triggered by microbial patterns and pathogen effectors via acting on the same target cell, adjacent cells, or distant cells. In addition, some phytocytokines could modulate plant physiological processes. Meanwhile, pathogens could mimic plant endogenous peptides to promote parasitism. In this talk, I will present data to discuss the perception and mode-of-actions of phytocytokines perceived by cell surface receptors in plant-microbe interaction and environmental stress adaptations. I will also discuss the pathogen-host evolutionary mimicry of immunomodulatory phytocytokines.