High-Performance Liquid Chromatography (HPLC) is a widely applied analytical technique for the development and validation of methods used in the quality control of Active Pharmaceutical Ingredients (APIs). Reliable analytical procedures are essential to ensure the identity, purity, potency, and stability of APIs throughout manufacturing and storage. This review discusses systematic approaches to HPLC method development, including selection of column, mobile phase optimization, detection wavelength determination, and optimization of chromatographic parameters. It further highlights essential validation characteristics such as specificity, linearity, accuracy, precision, robustness, and system suitability in accordance with regulatory guidelines. The application of HPLC in assay determination, impurity profiling, stability studies, and dissolution testing is also summarized. Recent advancements including UPLC, LC–MS integration, green analytical approaches, and automation are addressed to emphasize modern trends in pharmaceutical analysis. Overall, validated HPLC methods play a crucial role in ensuring regulatory compliance, product consistency, and patient safety in pharmaceutical quality control. Keywords: Active Pharmaceutical Ingredient (API), High-Performance Liquid Chromatography (HPLC), Method Development, Method Validation, Quality Control, Impurity Profiling, Stability Studies, Regulatory Compliance