© 2016 Elsevier Inc.Purpose To describe and compare the clinical and imaging characteristics of pigment epithelial detachments (PEDs) in age-related macular degeneration (AMD), polypoidal choroidal vasculopathy (PCV), and central serous chorioretinopathy (CSC) as seen in a clinical setting of a tertiary retinal practice. Design A perspective supported by clinical and imaging characteristics of a consecutive cohort of patients with strictly defined PEDs. Results One hundred seventy-four eyes of 113 patients with PEDs were studied with comprehensive clinical retinal examination and multimodal imaging; PEDs were differentiated into nonvascularized and vascularized forms with 3 main underlying etiologies: AMD (76%), PCV (9%), and CSC (3%). AMD was the most common diagnosis, with both nonvascularized PEDs (drusenoid and serous) and vascularized PEDs (type 1 and type 3 neovascularization) associated with drusen and a thin choroid. PCV patients had large, vascularized, peaked PEDs associated with polyps and a variable choroidal thickness, while CSC patients had a thick choroid and predominantly nonvascularized, serous PEDs with an overlying neurosensory detachment. The combined clinical and imaging characteristics form a profile for each PED subtype related to their underlying disease. However, atypical features noted in 11% of patients may complicate the underlying diagnosis. Conclusion Typical phenotypic manifestations of PEDs and other features seen with multimodal imaging were associated with specific underlying etiologies. As suggested by our study, identification of these features help clinicians to determine the precise underlying etiology and manage both vascularized PEDs, where evidence-based treatment exists, and nonvascularized PEDs, where current treatment is not supported by convincing evidence.