This chapter presents a systematic approach to troubleshooting in high-performance liquid chromatography (HPLC) systems, focusing on accurate problem identification and corrective action. It outlines common operational issues such as absence of peaks, flow interruptions, abnormal pressure, variable retention times, loss of resolution, peak distortion (tailing, fronting, splitting), baseline drift, noise, ghost peaks, and changes in selectivity or peak height. For each problem, probable causes and practical remedies are provided, enabling efficient isolation of faults related to pumps, detectors, injectors, columns, and mobile phase composition. The chapter emphasizes column maintenance and restoration, detailing cleaning and regeneration procedures for various column types, including silica-based reversed phase and ion exchange columns. It also discusses solvent properties, effects of polar solvents on silica columns, leak prevention, seal maintenance, and frit replacement. Overall, the chapter serves as a concise practical guide for maintaining optimal HPLC performance and ensuring reliable analytical results.