Throughout the life cycle of a plant, numerous responses need to be carefully regulated to ensure proper development and appropriate responses to external stimuli, and plant hormones play a crucial role in this regulation. Since the early 1990s, there has been expansive research elucidating the central role that peptide ligands play as intrinsic short- and long-distance communicators during development and as regulators of phenotypic plasticity. In this review, we focus on recently discovered mechanisms that ensure correct spatial and temporal cellular responses triggered by peptide ligands and provide examples of how peptide processing proteins and apoplastic conditions can regulate peptide activity in a timely manner.