This chapter reviews studies about egg-laying in the cuttlefish Sepia officinalis. Egg masses are spawned in specific mating and spawning coastal areas where mates aggregate between April and June in the English Channel and all year long in the Mediterranean Sea. Environmental cues are clearly involved in the aggregation process, but chemical communication also plays a determining role in these complex mechanisms. The successive steps of egg-laying are orchestrated by three classes of regulatory peptides: (1) neuropeptides that integrate environmental cues, (2) ovarian regulatory peptides that modulate the activity of the genital tract, and (3) sex pheromones expressed and released by the oviduct gland. After egg-laying, embryo protection is ensured for 8-10 weeks by a multilayer capsule secreted by the accessory sex glands. The oviduct gland secretes the inner layer of the egg case. The main nidamental gland secretes the main polysaccharides and glycoproteins, such as Sepia Egg Case Proteins, involved in capsule formation and in embryo protection. The accessory nidamental gland expresses specific proteins inherent in the structural organization of the gland, and hosts symbiotic bacteria. Similarly to salivary glands, this gland secretes immune factors possibly associated with gamete and/or embryo protection.