Mantle plumes originate at depths near the core−mantle boundary (~2,800 km). As such, they provide invaluable information about the composition of the deep mantle and insight into convection, crustal formation, and crustal recycling, as well as global heat and volatile budgets. In this Review, we discuss the effectiveness and challenges of using isotopic analyses of plume-generated rocks to infer mantle composition and to constrain geodynamic models. Isotopic analyses of plume-derived ocean island basalts, including radiogenic (Sr, Nd, Pb, Hf, W, noble gas) and stable isotopes (Li, C, O, S, Fe, Tl), permit determination of mantle plume composition, which in turn generate insight into mantle plume origins, dynamics, mantle heterogeneities, early-formed mantle reservoirs, crustal recycling processes, core−mantle interactions and mantle evolution. Nevertheless, the magmatic flux, temperature, tectonic environment and compositions of mantle plumes can vary. Consequently, plumes and their melts are best evaluated along a spectrum that acknowledges their different properties, particularly mantle flux, before making interpretations about the interior of the Earth. To provide insight into specific mantle and plume processes, future work should document correlations across elemental and isotopic data sets on the same sample powder, coordinate targeting sampling strategies, and refine stable isotopic fractionation factors through experiments. Such work will benefit from collaboration across geochemical laboratories, as well as among geochemists, mineral physicists, seismologists and geodynamicists.