Four new petrogenetic and metallogenic models are proposed herein to explain the formation of important mineral deposits in the Grenville Province, providing a framework from which to reappraise Grenvillian mineral potential. Recognition of a high-pressure metamorphic belt within the Grenville Province suggests a potential for eclogite-hosted rutile deposits, an important and much-sought commodity. A recently developed Norwegian model proposes that anorthosite genesis occurred through lower crust underplating and coeval partial melting, rather than by plume magmatism. Applied to the Grenville Province, the new petrogenetic model may provide insight into the widespread occurrence of platinum group element (PGE) poor nickel showings and the distribution of chromite, Ti-rich, and low-Ti iron-oxide deposits within the Grenville and adjacent terranes. A new type of sedimentary–exhalative (SEDEX) mineralization formed by oxidized brines has been defined following the discovery of new deposits in Australia. Applied to the Grenville Province, it provides a possible explanation for two long-recognized features of marble-hosted zinc deposits: (i) the presence of meta-siderite beds occurring as distal haloes around SEDEX zinc deposits, and (ii) the mutually exclusive division of these SEDEX deposits into massive sulphide and nonsulphide groups. The discovery of the giant Olympic Dam iron-oxide copper–gold (IOCG) deposit in Australia renewed the interest in magmatic low-Ti iron-oxide deposits in the Grenville Province that have been known and mined since early colonial times. Subsequent exploration in the northeastern part of the Grenville Province revealed the presence of breccia-hosted Cu–Au–U – rare-earth element (REE)-bearing iron-oxide mineralization. This deposit and other low-Ti iron-oxide deposits in the southwestern Grenville Province have a previously undocumented close spatial and temporal association with Ti-rich iron-oxide deposits. These examples demonstrate how new petrogenetic, tectonic, and ore deposit models developed in unmetamorphosed rocks can be successfully adapted to high-grade terranes, where they stimulate mineral exploration in these challenging conditions. Furthermore, by tracking the formation of ore deposits in the lower crust, the existence of unsuspected metallogenic associations in the higher crust, such as the low-Ti and high-Ti iron-oxide association observed in the Grenville Province, may be revealed.