Coral reefs are often considered as the proverbial canary in the mine for the oceans. Their current decline alarmingly correlates with indirect and direct anthropogenic stress resulting in increased frequencies and geographic spread of mass mortality, i.e., �coral bleaching�, and disease events. Thus, a rapid advancement in the understanding of the factors determining coral health and disease is of great importance. The post-genomic era has propelled both the development of high-throughput technologies and a shift in biological research from reductionist to system-level approaches. By viewing an organism as an �integrated and interacting network of genes, proteins, and biochemical reactions�, the nascent field of systems biology seeks to understand biological processes at a holistic level. In this dissertation, corals are considered as superorganisms, or �holobionts�, i.e., biological entities composed of a host organism and all of its associated microorganisms. The microbial component has been shown to play key roles in the functioning of the coral holobiont, but much remains to be studied about its 1) diversity, 2) response to stress, and 3) influence on the physiology, ecology, and evolution of the host. To address these gaps, I have applied a combinatorial approach of 454-sequencing, microbial community profiling (Phylochip), algal and host genotyping, as well as cDNA microarrays. The results include the most comprehensive census of coral-associated bacteria so far and illustrate that corals provide specialized habitats for an extremely diverse consortium of bacteria, including taxa that are often unknown, as well as rarely or not detected in the seawater. In diseased corals, bacterial communities profiles shifted and displayed a higher abundance of bacteria that are commonly found in other diseased marine invertebrates. Finally, correlating algal genotype and coral host transcriptomic data revealed a substantial interaction between microbial symbionts and host gene expression. These results represent initial efforts towards capturing the parts lists, i.e., the microbial diversity in coral holobionts, and integrating them with host transcriptomic data. The relevance of the results are discussed in the context of an envisioned coral (eco)systems biology approach to advance our understanding of coral health and disease.