In modern times a relationship between tuberculosis (TB) and rheumatoid arthritis (RA) has been firmly recognized, and is primarily attributable to the immunosuppressive therapies used to treat RA. Whereas TB can complicate the successful management of RA, nontuberculous mycobacteria have now perhaps become as important as (if not more so than) TB in the setting of RA, and can represent an even greater challenge to the rheumatologist wishing to use immunosuppressive therapies. This article reviews our most recent understanding of the epidemiological and clinical aspects of mycobacterial disease as it relates to RA, and the existing and emerging immunosuppressive therapies used to treat this disease.