The Plio-Quaternary magmatism in the Tyrrhenian Sea area exhibits wide compositional variations, which cover almost entirely those observed for volcanic rocks worldwide. Some volcanoes (Etna, Iblei, Sardinia, etc.) range from tholeiitic to Na-alkaline, and display elemental and isotope signatures typical of FOZO and EM-1 ocean-island basalts (OIB). Other volcanoes (Aeolian Arc, Italian peninsula) range from calc-alkaline–shoshonitic to K-alkaline, exhibit typical ‘subduction-related’ trace element signatures (low Ta–Nb, high Rb–Cs–LREE), and show a large range of radiogenic isotope ratios, from mantle-like in the Aeolian Arc to crustal-like in central Italy. Geochemical data suggest that OIB-type magmatism originated in lithosphere–asthenosphere sources that were unaffected by recent subduction. In contrast, subduction-related magmas come from mantle sources that underwent Eocene to present mixing with various amounts and types of subducted crustal components. Fluxing of the mantle wedge by water-rich fluids from a mid-ocean ridge basalt-type slab occurred in the southern Tyrrhenian Sea, whereas interaction between peridotite and various types of sediments occurred in central Italy. These contrasting styles of mantle contaminations relate to the nature (oceanic or continental) of the foreland, slab geometry and pre-metasomatic mantle compositions, which vary greatly along the Apennine arc and are the reason for the formation of the wide variety of orogenic magmas in Italy.