E-beam inspection provides a complementary approach to brightfield inspection for detection of otherwise difficult to detect physical defects. Advantages of E-beam inspection include superior resolution, the ability to classify defects using patch images and automatic filtering of prior level defects.A key limitation, however, is throughput. Therefore brightfield inspection should always be used for defection of physical defects when effective. For challenging defects, E-beam inspection data may be used as a gold standard for development of the best optical inspection conditions. For very challenging defects, it may be necessary to rely on E-beam inspection. An efficient inspection should be developed. Three examples are presented of challenging defects to illustrate the usefulness of E-beam inspection for physical defect detection.