Forty years ago, 12-oxophytodienoic acid (12-OPDA) was reported as a prostaglandin (PG)-like metabolite of linolenic acid found in extracts of flaxseed. Since then, numerous studies have determined the role of 12-OPDA in regulating plant immunity, seed dormancy, and germination. This review summarizes our current knowledge of the regulation of 12-OPDA synthesis in the chloroplast and 12-OPDA-dependent signaling in gene expression and targeting protein functions. We describe the properties of OPDA that are linked to the activities of PGs, which are derived from arachidonic acid and act as tissue hormones in animals, including humans. The similarity of OPDA with bioactive PGs is particularly evident for the most-studied cyclopentenone, PG 15-dPGJ2. In addition to chemical approaches towards 12-OPDA synthesis, bio-organic synthesis strategies for 12-OPDA and analogous substances have recently been established. The resulting availability of OPDA will aid the identification of additional effector proteins, help in elucidating the mechanisms of OPDA sensing and transmission, and will foster the analysis of the physiological responses to OPDA in plants. There is a need to determine the compartmentation and transport of 12-OPDA and its conjugates, over long distances as well as short. It will be important to further study OPDA in animal and human cells, for example with respect to beneficial anti-inflammatory and anti-cancer activities.