Infectious disease concerns are paramount when considering the health of the oceans and seas of the world. Understanding the ecology of disease in marine environments requires knowledge of diagnostic principles and techniques. Morphologic and molecular approaches exist that allow for the detection of infectious agents from marine life and from the marine environment. However, detection of infection may not be the equivalent of a diagnosis of disease. Disease determination requires recognition of anatomic, biochemical, and molecular features that are characteristic of the disease state and that identify pathogenic organisms. Disease investigations in marine scenarios can be complex and may engage concurrently a wide variety of techniques including microbiological culture and isolation, histotechnological procedures performed on arrays of tissue samples, immunohistochemical methodologies, and nucleic acid-based techniques that make use of genetic, genomic, transcriptomic, and metagenomic data. Effective use of these techniques requires knowledge of their capabilities and limitations so that appropriate selection, proper application, and accurate interpretation can be made.