Biliary strictures arise from diverse benign and malignant etiologies, and accurate differentiation is pivotal for prognosis and treatment selection. Conventional endoscopic retrograde cholangiopancreatography (ERCP)-based sampling (brush cytology and forceps biopsy) suffers from limited sensitivity despite high specificity, leaving a substantial proportion as indeterminate biliary strictures. Peroral cholangioscopy (POCS) enables direct intraductal visualization and targeted biopsies, thereby enhancing diagnostic yield. This review summarizes technological evolution from fiber-optic mother–baby systems to digital single-operator cholangioscopy and direct POCS, as well as the integration of image-enhanced endoscopy and emerging wide-channel scopes. Visual criteria for malignancy—tumor vessels, irregular granular or papillary/villous patterns, and friability—achieve high sensitivity and interobserver reliability with proposed classifications (Monaco, Mendoza). For cholangiocarcinoma, POCS-guided mapping biopsies precisely assess longitudinal intraepithelial tumor spread, informing R0 surgical planning. Randomized trials indicate higher or at least comparable sensitivity of POCS-guided biopsies relative to ERCP sampling, while novel forceps and larger working channels increase specimen size and reduce the number of biopsies. Artificial intelligence (AI) applied to POCS images shows promise for real-time risk stratification and improved targeting. Therapeutically, POCS guides intraductal lithotripsy with high clearance rates, and facilitates management in surgically altered anatomy in concert with endoscopic ultrasound-guided biliary drainage or transendosonographically/ guided created route procedure. Adverse events, chiefly pancreatitis and cholangitis, warrant attention to intraductal pressure control and CO2 insufflation. POCS has established an essential role in the diagnostic algorithm for biliary strictures; future advances will likely come from enhanced imaging, AI assistance, and next-generation digital cholangioscopes with larger biopsy devices.