There is no definitive cure for Mycobacterium avium subsp. paratuberculosis (MAP) infections, but several therapeutic agents may be used to alleviate clinical signs of Johne’s disease (JD) in ruminants of significant value. Treatment has to be maintained for the life of the animal and treated animals usually continue to shed MAP. No drugs are approved for treatment of JD in the United States; any drug use is “extra-label.” Isoniazid, rifampin, and clofazimine are most commonly used for treatment. Monensin, may aid in the prevention of infection in calves and to lower MAP fecal shedding in infected adult cattle.