Angio-oedema is a common reason for attendance at the accident and emergency department and for referral to immunology/allergy clinics. Causative factors should always be sought, but a large proportion of patients have the idiopathic form of the disease. A minority of patients represent a diagnostic and treatment challenge. Failure to identify the more unusual causes of angio-oedema may result in life-threatening situations. Common and rare causes of angio-oedema will be discussed in this article, as well as the diagnostic and treatment pathways for the management of these patients. A comprehensive history and close monitoring of response to treatment are the most cost-effective diagnostic and treatment tools.