Octocorals (Cnidaria, Octocorallia) constitute a geographically widely distributed and common group of marine invertebrates commonly referred to as “soft-corals,” “sea fans,” “horny corals,” “sea feathers,” and “sea plumes.” They are found from shallow coastal habitats to mesophotic and abyssal depths. Octocorals are important members of most Atlantic-Caribbean, Indo-Pacific, and Mediterranean coastal and mesophotic reef communities; however, information about their susceptibility to diseases, predation, and competition, and their relationship with changing environmental conditions is limited. At least 19 diseases have been observed in at least 42 common octocoral species throughout their range. Twelve of these have been reported in the wider Caribbean (CA), one in Brazil (BR), two in the Mediterranean (ME), one in the Eastern Pacific (EP), and three in the western Pacific (WP). Pathogenic and/or environmental causes have been identified for eight diseases, including viruses, terrestrial fungi, protozoans, bacteria and cyanobacteria, filamentous algae, parasitic copepods, and high temperature. Only a few of the suspected pathogens have been tested with Koch’s postulates. At least eight disease outbreaks have led to extensive octocoral mortalities in the CA, ME, BR, and EP with detrimental ecological consequences. The fungal disease Aspergillosis has produced the highest mortalities in the CA and the EP. Other fungi, protozoans, and the bacterium Vibrio coralliilyticus were identified as potential causes of the death of millions of colonies in two Mediterranean disease outbreaks. Bacterial and fungal agents seemed to be responsible for the mass mortalities in Brazil and the WP. Most outbreaks in all regions were linked to high thermal anomalies associated with climate change, which seems to be the major driver. Other biological stressors such as predation and/or competition produce injuries that may contribute to the spread of infections and mortality. Overfishing of common predators could lead to population explosions of octocoral-feeding species that produced mass mortalities in some Caribbean localities. Our lack of knowledge of causes and pathogenesis of octocoral diseases parallels that of hard corals. New diseases are being described almost every year concomitant with increasing seawater temperatures. The ecological and economic consequences could be significant, with drastic changes in the seascape of shallow coral reefs and other coastal marine habitats and reduction of their ecological services. Given our limited knowledge, our best options for recovery of octocorals and coral reefs in general include sound management of coastal fisheries, development and tourism; reduction of land- and sea-based pollution; and abating effects of climate change.