The threat of mycobacterial zoonotic transmission (particularly bTB) has driven expensive eradication efforts and large culling projects. In the absence of reliable vaccines however, the cost and complexity of programs needed to secure eradication from domestic herds and wildlife maintenance reservoirs has had limited progress. Few have succeeded in eradication and some arguably increased transmission rates. As a result bTB and MAP remain prevalent in domestic animals and wildlife reservoirs. Given the opportunity and a favorable host susceptibility these mycobacteria can cause disease in humans. Acute bTB infection is a potentially life threatening disease clinically indistinguishable from tuberculosis. Pasteurization remains an effective defense reflected by the fact that most human bTB cases are either a result of direct animal contact or re-activation from an older latent infection. For MAP, the issue is less clear cut. Despite significant indications that MAP invades, is present and persistent in many humans and has the capacity in susceptible individuals to trigger inflammatory bowel conditions such as Crohn’s disease, the role of MAP as a direct human pathogen is still not widely accepted. Worryingly MAP survives pasteurization and prevalence is such that viable MAP is now significantly present in retail and dried infant formula milk. If MAP is truly a human pathogen, current ineffectual MAP control methods are permitting an extensive, unchecked, worldwide, chronic exposure to humans, some of whom are susceptible to developing disease. Latency and persistence are important characteristics of mycobacterial disease evoking long term immunological influences promoting disease. These states have been difficult to quantitate due to dormant unculturable phenotypes. Better tests are needed but the likelihood is that the extent of bTB and MAP disease burden in humans is not yet fully evident. The threat from bTB and MAP to human health thus remains tangible. Only vigilance currently prevents many potential animal reservoirs becoming re-seeded. Failure to improve screening and eradication tools will continue to allow global spread, increase the risk of human exposure and ensure more trouble is in store.