Odorant receptors (ORs) are transmembrane proteins expressed in animal olfactory sensory neurons. They are at the core of odorant detection since they recognize odorants and trigger a neuronal response that will be transmitted to the central nervous system. However, most of these ORs are still orphans, which means the odorants that activate them are unknown. The so-called “reverse chemical ecology” or “molecular chemical ecology” approaches propose to use OR-ligand and/or OR-sequence characteristics to identify potential new ligands via a combination of modelling and experimentation, which have the potential to accelerate the discovery of new ligands. Using the crop pest moth Spodoptera littoralis (Lepidoptera; Noctuidae), we used such approaches for the study of insect ORs. Ligand-based virtual screening coupled to experimental validation led us to extend the range of semiochemicals active at the receptor and the behavioural levels. Our work opens new routes for i) odorant receptor function analysis, ii) a better understanding of this species odor space, and iii) the development of novel insect pest control strategies targeting chemosensory receptors.