Metrosideros polymorpha Gaud. (‘ōhi‘a) is the most abundant native forest tree in Hawai‘i and a keystone species of cultural, ecological, and economic importance. ‘Ōhi‘a forests, particularly on Hawaiʻi Island, are being severely impacted by Rapid ‘Ōhi‘a Death (ROD), which is caused by the fungal pathogens Ceratocystis lukuohia and C. huliohia. ROD is characterized by branch dieback, crown wilting, and mortality. Initial disease resistance screening of four varieties of M. polymorpha with C. lukuohia demonstrated that varieties may differ in susceptibility. Several survivors of field or screening-based infections still exist, providing strong impetus for the establishment of the ‘Ōhiʻa Disease Resistance Program (ʻŌDRP). Here, we outline a framework for guiding the ʻŌDRP throughout the process of identifying and developing ROD resistance in M. polymorpha and, possibly, all Hawaiian Metrosideros species. Core ʻŌDRP projects include: (1) evaluating and operationalizing methods for greenhouse-based production and screening of test plants; (2) greenhouse screening of seedlings and rooted cuttings sampled from native Metrosideros throughout Hawaiʻi; (3) establishing field trials to validate results from greenhouse assays; (4) understanding environmental and genetic drivers of resistance to characterize the durability of resistance to ROD; (5) developing remote sensing and molecular methods to rapidly detect ROD-resistant individuals; and (6) conducting breeding trials to improve the degree and durability of ROD resistance. Ultimately, the ʻŌDRP seeks to produce ROD-resistant material for the perpetuation of M. polymorpha across Hawai‘i, with the goal of preserving the ecology, culture, and communities that are dependent on this tree species.