We report the successful treatment of disseminated Mycobacterium intracellulare osteomyelitis, without evidence of other visceral involvement, in a previously healthy, HIV-negative, 2-year-old female using a 23-month regimen of antimicrobial agents that included 18 months of oral therapy with azithromycin, rifabutin, trimethoprim-sulfamethoxazole (TMP/SMX), and ethambutol.