The structural three-dimensional (3D) search of the structural database has become a very effective approach for the discovery of new lead compounds in drug discovery. Although several commercial programs are available, these commercial programs are mainly used as a stand alone and require a local database. In recent years, the Internet has become the main means of choice for the distribution of multi-user application programs. At every stage of the drug discovery process, searching for 3D databases can play an important role. Medicinal chemicals have many tools in their arsenal to assist in the early stages of a new project, and searching for 3D databases is now an essential part of the drug discovery process. To meet the challenges of the next millennium in the pharmaceutical industry, the time needed to find clues to initiate research into new therapeutic areas should be as short as possible. 3D database search offers a way to achieve that success.