The management of fire-dependent biodiversity hotspots must be based on sound ecological knowledge and a pragmatic approach that accommodates the constraints within which fire managers must operate. South Africa’s fynbos biome (shrubland or heathland vegetation found in the Western Cape of South Africa) is one such hotspot. In this region, the implementation of prescribed burning to conserve biodiversity must take into account the area’s rugged and inaccessible terrain and recurrent wildfires, the presence of fire-adapted invasive alien plants, and the imperatives for ensuring human safety. These constraints limit the potential for prescribed burning to be effective everywhere, and prioritization and trade-offs will be needed to ensure the efficient use of limited funding and management capacity. In such environments, management must be adaptive, based on clearly defined and shared goals, monitoring, and assessment, and should be flexible enough to adjust as new lessons are learned.