The quality, safety, and efficacy of pharmaceutical products are critically dependent on their stability and proper analytical evaluation. Antibiotic drugs, particularly Ciprofloxacin, are widely used in the treatment of bacterial infections and must maintain their therapeutic effectiveness throughout their shelf life. However, degradation due to environmental factors such as temperature, light, humidity, and pH can significantly affect drug potency, leading to reduced efficacy and potential safety concerns. In recent years, increasing attention has been given to the evaluation of pharmaceutical products beyond their labeled shelf life, especially due to the practical use of expired medications in certain conditions.This review focuses on the application of Reverse Phase High-Performance Liquid Chromatography (RP-HPLC) as a reliable and widely accepted analytical technique for the estimation of antibiotic drugs in pharmaceutical formulations. The paper discusses various aspects of method development and validation in accordance with ICH guidelines (Q2(R1)), including parameters such as specificity, linearity, accuracy, precision, limit of detection, limit of quantification, robustness, and ruggedness. Additionally, the importance of forced degradation studies in the development of stability-indicating methods is highlighted, with emphasis on different stress conditions such as acidic, basic, oxidative, thermal, and photolytic degradation