Mycobacteriosis is a widespread, chronic disease of estuarine fishes. Recent studies by scientists at the National Fish Health Research Laboratory, Leetown, West Virginia and the Virginia Institute of Marine Science, Gloucester, have shown infection rates in striped bass (Morone saxatilis) of up to nearly 62% in certain Virginia tributaries to Chesapeake Bay (Bay). Of the several mycobacterial species known to infect striped bass from the Bay, several are known to be zoonotic including M. marinum and M. fortuitum. In this paper we discuss the incidence and prevalence of mycobacterial infections in striped bass and contrast these with human epidemiological data on the occurrence of cutaneous mycobacteriosis in the Bay's human population collected by the Virginia Department of Health and the Maryland Department of Health. During a period from 1995-2005, the Commonwealth of Virginia (VA) and State of Maryland (MD) collectively documented 275 cases of non-tuberculosis mycobacteria (NTM) infections by M. marinum in the human population within the Bay watershed. The data indicates that most of the persons infected were males (67%-VA; 67%-MD) between the ages of 40 and 70 (79%-VA; 62%-MD) and that most infections occurred on fingers and hands (43%-VA 63%-MD). During the same 10-year period, only four cases of NTM infection were recorded in 11 non-Bay counties from both states combined. While cause-and-effect relationships cannot be clearly demonstrated between the epizootic of mycobacteriosis in striped bass and these elevated incidences of NTM cutaneous infections in the human population of the Bay counties, the weight-of-evidence suggests reason for concern. Based on these concerns, a workshop of federal, state and academic researchers and managers was convened in May 2006 in Annapolis, Maryland, to develop an adaptive management framework of both short-term and long-term resources management needs. These proposed research and management actions were predicated on understanding the etiology of the infectious disease and having effective communication networks in place for sharing information, making decisions, and sharing information among fishery managers, public health officials and veterinarians.