Multiple infiltrative disorders can affect the small bowel, often resulting in diffuse small bowel wall thickening. These infiltrative disorders can manifest owing to various factors such as an influx of immunologic or neoplastic cells or the accumulation of substances within one or more layers of the intestinal wall. Although there can be considerable overlap in the appearances of infiltrative diseases on cross-sectional images, a comprehensive understanding of more specific ancillary imaging features and clinicopathologic correlation can substantially narrow the differential diagnosis. The radiologist can be instrumental in synthesizing the clinical and imaging information and guiding subsequent workup. The authors present a comprehensive review of the infiltrative disorders that commonly involve the small bowel. These disorders are organized on the basis of their pathophysiologic features, with multiple illustrative case examples to enhance understanding of these entities. CT and MRI are currently the most commonly used imaging modalities for evaluating small bowel disorders, and this review is focused on these two modalities. Detailed information regarding the pathologic features, clinical presentation, and imaging findings of these infiltrative disorders is provided to aid radiologists in recognizing and differentiating these conditions. ©RSNA, 2024.