During the past decade, a flurry of research focusing on the role of peptides as short- and long-distance signaling molecules in plant cell communication has been undertaken. Here,we focus on peptides derived from nonfunctional precursors, and we address several key questions regarding peptide signaling. We provide an overview of the regulatory steps involved in producing a biologically active peptide ligand that can bind its corresponding receptor(s) and discuss how this binding and subsequent activation lead to specific cellular outputs. We discuss different experimental approaches that can be used to match peptide ligands with their receptors. Lastly, we explore how peptides evolved from basic signaling units regulating essential processes in plants to more complex signaling systems as new adaptive traits developed and how nonplant organisms exploit this signaling machinery by producing peptide mimics.