Molecular docking is a powerful tool in structure-based drug discovery. This review discusses available docking methods, their development, and applications. It covers basic theories, including sampling algorithms and scoring functions, and discusses the performance of docking software. Flexible receptor docking remains a challenge, but the Local Move Monte Carlo (LMMC) approach is introduced as a potential solution. Three application examples are provided, including the identification of DNA gyrase inhibitors, validation of docking in cytochrome P450 proteins, and comparison of virtual screening and high-throughput screening for PTP-1B inhibitors. The review highlights the importance of scoring functions, which are crucial for predicting binding affinities. It also discusses the challenges of receptor flexibility and the need for efficient computational methods. The LMMC approach is proposed as a method for sampling ligand conformations in loop-containing active sites. The review concludes that while docking is a valuable tool, it is not standalone and is often used in combination with other techniques. The development of more accurate and efficient scoring functions is essential for improving docking applications.Molecular docking is a powerful tool in structure-based drug discovery. This review discusses available docking methods, their development, and applications. It covers basic theories, including sampling algorithms and scoring functions, and discusses the performance of docking software. Flexible receptor docking remains a challenge, but the Local Move Monte Carlo (LMMC) approach is introduced as a potential solution. Three application examples are provided, including the identification of DNA gyrase inhibitors, validation of docking in cytochrome P450 proteins, and comparison of virtual screening and high-throughput screening for PTP-1B inhibitors. The review highlights the importance of scoring functions, which are crucial for predicting binding affinities. It also discusses the challenges of receptor flexibility and the need for efficient computational methods. The LMMC approach is proposed as a method for sampling ligand conformations in loop-containing active sites. The review concludes that while docking is a valuable tool, it is not standalone and is often used in combination with other techniques. The development of more accurate and efficient scoring functions is essential for improving docking applications.