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Prolonged therapy with isoniazid is used for the treatment of pulmonary tuberculosis. Drug-induced lupus erythematosus is a rare, adverse event associated with isoniazid use and can complicate treatment, especially if it is associated with pneumonitis. The diagnosis is made by clinical suspicion, elevated serum titers of anti-nuclear antibody and anti-histone antibody, and new ground-glass opacities on chest tomography. Bronchoscopy with bronchoalveolar lavage and transbronchial biopsy of affected areas of the lung is useful to increase diagnostic accuracy and differentiate between drug-induced pneumonitis, concomitant infection, or other inflammatory processes. Treatment includes systemic corticosteroids and cessation of isoniazid therapy.