Many chemists think in terms of structure rather than using textual representations of the substances that they study. Reaction schema are laid out using structures; and ChemDraw figures, as well as crystal structures, efficiently demonstrate the structure of a new molecule or complex. These structures and reactions are indexed by database creators and can be used as entry points to the primary literature. Chemical structures have been represented in a machine-searchable manner for 50 or 60 years but, prior to the 1980s or 1990s, the complex method in which they were represented in the secondary sources made it difficult for anyone but a trained information professional to search using them. However, in recent years, graphical user interfaces have made structure searching accessible to anyone who is able to draw a structure using ChemDraw or a similar structure editor, and structure search interfaces have popped up everywhere from the Aldrich Catalog to the CAS Registry, via SciFinder® or STN. This chapter will discuss techniques of performing effective structure searches, as well as methods of searching for substances containing a desirable core or fragment. Readers interested in learning more about historic methods of representing chemical structure for information retrieval, can refer to Wendy Warr's 2011 review article, which synthesizes the important changes in methodology and technology from the 1950s to the present day.