Hilar biliary strictures (HBS) are difficult to diagnose and treat, because their etiology is not always ascertained by all the available diagnostic tests. If a diagnosis cannot be made, HBS are classified as indeterminate. In recent years, both new imaging and endoscopic techniques, and a better understanding of hepato-biliary diseases have significantly reduced the number of patients diagnosed with indeterminate HBS. A complete work-up of these patients is mandatory to exclude malignancy and is based on laboratory tests, radiological imaging, and endoscopic procedures. Briefly, a decision-making process for the diagnosis of patients with HBS is discussed and a diagnostic algorithm is proposed.