Physicians confronted with a patient with an interstitial lung disease (ILD) face a number of major problems. First, its prognosis can range from death within weeks to complete recovery, and clarifying these outcomes for any individual patient is crucial. We currently stratify an individual’s prognosis by defining clinico-radiographic-pathologic syndromes. Making a definitive diagnosis of one of these syndromes generally requires information from each of the clinical, radiographic, and pathologic pieces, with the data obtained by surgical lung biopsy providing the most authoritative information. However advances in high-resolution CT (HRCT) technology have forced a second problem: when is a surgical lung biopsy, with its attendant risk of complication, necessary for diagnosis? Thirdly, even when obtained, surgically obtained lung tissue may not be diagnostic and may even be difficult to classify according to current criteria. What is to be done in these circumstances? Lastly, the treatment options (irrespective of the underlying etiology or histology) are often associated with significant side effects, are of limited efficacy, or are both. The answer to these problems has eluded clinicians for decades.