Biologic drugs have revolutionized the treatment of certain hematologic, autoimmune, and malignant diseases, but they may place patients at risk for reactivation or acquisition of tuberculosis. This risk is highest with the tumor necrosis factor-alpha (TNF-α) inhibitors. Amongst this class of drugs, the monoclonal antibodies (infliximab, adalimumab, golimumab) and antibody fragment (certolizumab) carry an increased risk compared to the soluble receptor fusion molecule, etanercept. Treatment of latent TB is critical to decrease the risk of reactivation. Data continues to emerge regarding tuberculosis risk associated with novel biologics targeting cytokines involved in tuberculosis control.