Diseases threaten corals globally, but 40 years on their causes remain mostly unknown. We hypothesize that inconsistent application of a complete diagnostic approach to coral disease has contributed to this slow progress. We quantified methods used to investigate coral disease in 492 papers published between 1965 and 2013. Field surveys were used in 65% of the papers, followed by biodetection (43%), laboratory trials (20%), microscopic pathology (21%), and field trials (9%). Of the microscopic pathology efforts, 57% involved standard histopathology at the light microscopic level (12% of the total investigations), with the remainder dedicated to electron or fluorescence microscopy. Most (74%) biodetection efforts focused on culture or molecular characterization of bacteria or fungi from corals. Molecular and immunological tools have been used to incriminate infectious agents (mainly bacteria) as the cause of coral diseases without relating the agent to specific changes in cell and tissue pathology. Of 19 papers that declared an infectious agent as a cause of disease in corals, only one (5%) used microscopic pathology, and none fulfilled all of the criteria required to satisfy Koch’s postulates as applied to animal diseases currently. Vertebrate diseases of skin and mucosal surfaces present challenges similar to corals when trying to identify a pathogen from a vast array of environmental microbes, and diagnostic approaches regularly used in these cases might provide a model for investigating coral diseases. We hope this review will encourage specialists of disease in domestic animals, wildlife, fish, shellfish, and humans to contribute to the emerging field of coral disease.