Prescribed fire is widely accepted as a conservation tool because fire is essential to the maintenance of native biodiversity in many terrestrial communities. Approaches to this land-management technique vary greatly among continents, and sharing knowledge internationally can inform application of prescribed fire worldwide. In North America, decisions about how and when to apply prescribed fire are typically based on the historical-fire-regime concept (HFRC), which holds that replicating the pattern of fires ignited by lightning or preindustrial humans best promotes native species in fire-prone regions. The HFRC rests on 3 assumptions: it is possible to infer historical fire regimes accurately; fire-suppressed communities are ecologically degraded; and reinstating historical fire regimes is the best course of action despite the global shift toward novel abiotic and biotic conditions. We examined the underpinnings of these assumptions by conducting a literature review on the use of historical fire regimes to inform the application of prescribed fire. We found that the practice of inferring historical fire regimes for entire regions or ecosystems often entails substantial uncertainty and can yield equivocal results; ecological outcomes of fire suppression are complex and may not equate to degradation, depending on the ecosystem and context; and habitat fragmentation, invasive species, and other modern factors can interact with fire to produce novel and in some cases negative ecological outcomes. It is therefore unlikely that all 3 assumptions will be fully upheld for any landscape in which prescribed fire is being applied. Although the HFRC is a valuable starting point, it should not be viewed as the sole basis for developing prescribed fire programs. Rather, fire prescriptions should also account for other specific, measurable ecological parameters on a case-by-case basis. To best achieve conservation goals, researchers should seek to understand contemporary fire–biota interactions across trophic levels, functional groups, spatial and temporal scales, and management contexts.