This chapter explores the microorganisms that inhabit different components of the coral reef ecosystem in the Red Sea. Microbes play crucial roles in numerous reef processes, including primary production as well as nutrient and organic matter cycling. Microbes are also ubiquitous symbionts of eukaryotic organisms, providing the host with nutrients, chemical cycling, and defensive functions. The Red Sea is a particularly interesting study system due to its unusual physiochemical properties, such as a strong north-south temperature and salinity gradient. Here we examine the influence of these unusual characteristics on microbes in the water column and sediments, and those associated with corals, sponges, and fish. In the water column, the microbial community indeed appears to correlate with prevailing north-south environmental conditions. For example, heterotrophic picoplankton and the cyanobacteria Synechococcus tend to be more abundant in the warmer, less saline, southern waters. On the other hand, the microbes associated with corals, sponges, and fish seem to be conserved throughout the Red Sea and many other parts of the world. For example, several coral species in the Red Sea harbor Endozoicomonas bacteria, and this is also observed world-wide. Moreover, the dominance of Epulopiscium bacteria in surgeonfish and highly conserved microbial communities in sponges are also commonly reported in other regions. In terms of microbial-based diseases, Red Sea corals display many typical disorders, including white syndromes, skeletal eroding band, black band disease, and growth anomalies, but these are rare within Red Sea waters. Thus, despite strong environmental extremes driving free-living microbial communities in the Red Sea, the microbes in tightly regulated symbiotic environments appear to be conserved, although strain-level and genotype specialization are areas of continuing research.