Mesophotic coral ecosystems (MCEs), which comprise the light-dependent communities of corals and other organisms found at depths between 30 and ~150 m, have become a topic that increasingly draws the attention of coral reef researchers. It is well established that after the reef-building scleractinian corals, octocorals are the second most common group of macrobenthic animals on many shallow Indo-Pacific reefs. This chapter reviews the existing knowledge (e.g., species composition and depth of occurrence) on octocorals from selected Indo-Pacific MCEs: Okinawa (Japan), Palau, South Africa, the northern Red Sea, and the Great Barrier Reef (Australia). For all reefs, zooxanthellate taxa are not found below 65 m. We, therefore, suggest that physiological constraints of their symbiotic algae limit the depth distribution of zooxanthellate octocorals. More studies of lower MCEs (60–150 m) and their transition to deepwater communities are needed to answer questions regarding the taxonomy, evolutionary origins, and phylogenetic uniqueness of these mesophotic octocorals. New findings on mesophotic octocoral sexual reproduction indicate a temporal reproductive isolation between shallow and mesophotic octocoral populations, thus challenging the possibility of connectivity between the two populations. The existing data should encourage future studies aimed at a greater understanding of the spatiotemporal features and ecological role of mesophotic octocorals in reef ecosystems.