Diabetes can be a very difficult disease to manage. This is particularly true when confronted with a patient who attends with recurrent episodes of hypoglycemia, diabetic ketoacidosis, or mixed glycemic instability. This chapter aims to explain the common causes of such presentations, and the suitable investigations to identify a treatable cause. Further to this, if a diagnosis cannot be reached and the problems still persist, the chapter then discusses the diagnosis and management of “brittle diabetes.” This complex and often misunderstood disease affects only a very small minority of patients with type 1 diabetes but requires a considered and careful approach to its diagnosis and treatment. Such issues are discussed within this chapter.