Hypersensitivity pneumonitis is a diffuse, granulomatous interstitial lung disease caused by repeated exposure to a wide spectrum of environmental antigens. Clinical, radiologic, and histologic findings are quite variable and mimic many other diseases; therefore, diagnosis depends on a constellation of findings rather than a single defining feature. High-resolution computed tomography (HRCT) plays a critical role in this setting. The presence of centrilobular nodules, multifocal ground glass opacities, and evidence of air trapping in the expiratory phase of respiration is highly suggestive of hypersensitivity pneumonitis and can direct clinicians to the correct diagnosis. For the pathologist, typical HRCT findings not only corroborate the diagnosis of hypersensitivity pneumonitis when the characteristic triad of airway-centered chronic interstitial inflammation, interstitial poorly formed non-necrotizing granulomas, and organizing pneumonia is present on biopsy, but also improve diagnostic confidence in biopsies lacking components of the diagnostic histologic triad. Importantly, the presence of focal or unilateral imaging findings should prompt a careful search by the pathologist for an infectious etiology, thus avoiding errors in determining the significance of granulomas on biopsy. This article reviews the essential radiologic and pathologic findings in hypersensitivity pneumonitis, discusses the primary considerations in the differential diagnosis, and offers an approach to biopsy evaluation.