The location of magmatic Ni-Cu-PGE sulfide deposits is related to lithospheric architecture, particularly that of the subcontinental lithospheric mantle (SCLM). At crustal levels, this relationship is manifest by a close proximity to craton and paleocraton margins. Deposits are associated with mafic-ultramafic rocks and many show a close spatial relationship with a coeval large igneous province (LIP). Metal quantities and tenors observed in deposits require segregation of a magmatic sulfide melt from a large volume of parental ultramafic melt. Generation of these parental melts requires melting of upwelling mantle rising to depths of 100 km or less. The timing and tectonic setting of deposits indicates that this most likely occurs when mantle plumes impact on the base of the SCLM and are channeled laterally to areas of thinnest SCLM, where they undergo decompression melting. Alternatively, the setting of some smaller deposits suggests that upwelling may be induced by syn- to post-collisional lithospheric delamination. Craton margins are generally zones of relatively thin lithosphere and are the focus of strain during regional tectonism, providing points of dilation along active translithospheric faults. These faults facilitate melt introduction into the crust. The craton margin zone of thin lithosphere and active faulting may be adjacent to a neighboring block of continental lithosphere (paleocraton margin) or adjacent to a flanking narrow marginal basin (underlain by asthenosphere). All deposits form during periods of active regional tectonism, most commonly under mildly compressional to transpressional conditions. These different settings and conditions may result in differing depths of melting and differing depths and degrees of crustal interaction. The latter is believed to be a key factor for the development of a metal-rich sulfide melt, which is ultimately emplaced in the deposit environment. These variations can account for the observed range of ore and host rock types. Most large deposits are associated with intracontinental settings or with (former) passive margins at the edge of small marginal basins. No significant deposits are associated with the margins of large oceans or with suprasubduction zone environments, possibly reflecting poor preservational potential or (with the latter) limitations to plume interaction with continental lithosphere. A craton-margin model for the genesis of magmatic Ni-Cu-PGE deposits is proposed. This model provides a framework for further examination of deposit-forming processes and also provides a coherent predictive framework for mineral exploration.