Theophylline is a widely used bronchodilator for treating asthma-related symptoms like shortness of breath and chest tightness. However, its narrow therapeutic plasma range (20-200 μM) necessitates careful monitoring of blood levels to prevent toxicity. Various clinical laboratory techniques have been developed for detecting theophylline, including spectroscopy, high-performance liquid chromatography (HPLC), fluorescence polarization immunoassay, and radioimmunoassay. Despite their utility, these methods are limited by complex sample preparation, long processing times, large sample volumes, and high costs. Aptamer-based biosensors have emerged as a promising alternative, offering superior selectivity and specificity compared to conventional methods. This review evaluates the performance of aptamer-based sensors in terms of sensitivity, specificity, and limit of detection, comparing them to traditional techniques. Recent studies demonstrate the advantages of aptamer-based sensors, including their simplicity, rapid response time, and cost-effectiveness, which make them ideal for point-of-care applications. The review also explores the methodologies used in aptamer-based detection, highlighting key innovations and advances in the field. Findings from the literature show how aptamer-based sensors enhance the monitoring of theophylline levels, overcoming the limitations of traditional techniques. This is the first review dedicated to discussing aptamer-based techniques for theophylline monitoring, addressing a gap in current literature.