Thickening of the interlobular septa is a common and easily recognizable finding at high-resolution computed tomography (HRCT; 1-2 mm collimation high-spatial-frequency reconstruction algorithm). Interlobular septal thickening at HRCT can be smooth, nodular, or irregular in contour. It may be due to fluid, cellular infiltration, or fibrosis. Apparent thickening of septa at HRCT may also be due to abnormalities in the periphery of the secondary pulmonary lobule adjacent to but not involving the interlobular septa. This article illustrates the patterns of interlobular septal thickening at HRCT in various disease entities.