Sponges are the most simple and primitive metazoans, yet they have various biological and ecological properties that make them an influential component of coral-reef ecosystems. Marine sponges provide refuge for many small invertebrates and are critical to benthic-pelagic coupling across a wide range of habitats. Reports of sponge disease have increased dramatically in recent years with sponge populations decimated throughout the Mediterranean and Caribbean. Reports also suggest an increased prevalence of sponge disease in Papua New Guinea, the Great Barrier Reef and in the reefs of Cozumel, Mexico. These epidemics can have severe impacts on the survival of sponge populations, the ecology of the reef and the fate of associated marine invertebrates. Despite the ecological and commercial importance of sponges, the understanding of sponge disease is limited. There has generally been a failure to isolate and identify the causative agents of sponge disease, with only one case confirming Koch's postulates and identifying a novel Alphaproteobacteria strain as the primary pathogen. Other potential disease agents include fungi, viruses, cyanobacteria and bacterial strains within the Bacillus and Pseudomonas genera. There is some evidence for correlations between sponge disease and environmental factors such as climate change and urban/agricultural runoff. This review summarizes the occurrence of sponge disease, describes the syndromes identified thus far, explores potential linkages with environmental change and proposes a strategy for future research towards better management of sponge disease outbreaks.