Pharmaceutical analysis is critical in ensuring the quality and safety of drug substances and formulations. High-performance thin-layer Chromatography (HPTLC) has emerged as a powerful analytical technique in the pharmaceutical industry due to its numerous advantages, including high separation efficiency, cost-effectiveness, and ease of sample preparation. One of its variants, Reversed-Phase High-Performance Thin-Layer Chromatography (RP-HPTLC), has gained immense popularity for analyzing nonpolar and slightly polar compounds, including drugs and their metabolites. This review paper draws attention to history and the recent developments in RP-HPTLC for pharmaceutical analysis. It highlights the advantages and limitations of RP-HPTLC, discussing its applications in drug analysis, impurity determination, stability-indicating assays, and more. In this study, recent advances in RP-HPTLC instrumentation and techniques were reviewed, including hyphenated methods, such as Reversed-Phase High-Performance Thin-Layer Chromatography coupled with Mass Spectrometry and Reversed-Phase High-Performance Thin-Layer Chromatography coupled with Nuclear Magnetic Resonance. Through this comprehensive analysis, the authors aim to underscore the potential of RP-HPTLC as a reliable and efficient analytical technique in the pharmaceutical industry and shed light on future trends in this field.