In this course from AAO 2022, the instructors use diagnostically challenging cases to demonstrate the interpretation of color photographs, spectral-domain optical coherence tomography (OCT), OCT angiography, and fluorescein angiography. When indicated, indocyanine green angiography, fundus autofluorescence, enhanced depth imaging OCT, swept-source OCT, infrared images, wide-angle imaging, echography, electrophysiologic studies, microperimetry, computed tomography, magnetic resonance imaging, results of genetic studies, and cytology and/or histopathology are also shown. After completing the course, participants should be better able to assess and evaluate a variety of challenging retina cases, establish a more complete differential diagnosis, and make the best use of ancillary diagnostic tests to establish a diagnosis and formulate a definitive treatment plan.