The following policy guidelines are intended for use by health care professionals involved in the complex and difficult task of managing mono-and poly-resistant TB, MDR- and XDR-TB patients in South Africa. The guidelines focus on the clinical management, referral mechanisms and models of care. However, psychosocial support to ensure comprehensive management of the patients, strategies for infection prevention and control, and occupational health services for health care workers (HCWs) are covered.