Coldwater disease (CWD) is a bacterial disease that affects a broad host-species range of fishes that inhabit cold, fresh waters. This disease occurs predominately at water temperatures of 16 °C and below, and is most prevalent and severe at 10 °C and below. Coldwater disease occurs in cultured and free-ranging populations, with hatchery-reared young trout and salmon species especially vulnerable to infections. Flavobacterium psychrophilum is the etiological agent of CWD. This Gram-negative bacterium may be recovered from affected host tissues and characterized using standard biochemical techniques, providing that reduced nutrient media are used. There are numerous reports that describe sensitive and specific serologic and genomic diagnostic techniques for CWD. The entire genome of a virulent isolate of F. psychrophilum has been sequenced and described. Rainbow trout (Oncorhynchus mykiss) fry syndrome is also caused by F. psychrophilum with mortalities >50% possible among affected fish lots. Evidence suggests that pathogen transmission occurs both horizontally and vertically. Analogous to many diseases to other animals, prevention and control are essential to avoid losses to CWD, particularly since there is currently no commercially available vaccine and a limited number of antimicrobials have been approved for treating food fish worldwide. This review provides current host and geographic ranges of the pathogen, and covers epizootiology, transmission, pathogenicity, diagnostics, and prevention and treatment.