Hot spot–mid-ocean ridge interactions cause many of the largest structural and chemical anomalies in Earth's ocean basins. Correlated geophysical and geochemical anomalies are widely explained by mantle plumes that deliver hot and compositionally distinct material toward and along mid-ocean ridges. Compositional anomalies are seen in trace element and isotope ratios, while elevated mantle temperatures are suggested by anomalously thick crust, low-density mantle, low mantle seismic velocities, and elevated degrees and pressures of melting. Several geodynamic laboratory and modeling studies predict that the width over which plumes expand along the ridge axis increases with plume flux and excess buoyancy and decreases with plate spreading rate, plume viscosity, and plume-ridge separation. Key aspects of the theoretical predictions are supported by observations at several prominent hot spot–ridge systems. Still, many basic aspects of plume-ridge interaction remain enigmatic. Outstanding problems pertain to whether plumes flow toward and along mid-ocean ridges in narrow pipe-like channels or as broad expanding gravity currents, the origin of geochemical mixing trends observed along ridges, and how mantle plumes alter the geometry of the mid-ocean ridge plate boundary, as well as the origin of other ridge axis anomalies not obviously related to mantle plumes.