The One Health policy framework offers an appealing model to policy advocates disillusioned with the sustainable use narrative. Through membership of the African Union, South Africa has endorsed the One Health Approach, and the concept recently found renewed resonance in a major high-level government wildlife policy review. This work considers the One Health Framework in detail, arguing that the theoretical appeal of acknowledging the overlapping dependencies that unpin the framework is in practice entirely inadequate to arrest and reverse the destruction of the environment and the institutionalised suffering of animals. This is in part because the framework seeks to balance short-term easily quantifiable commercial benefits to humans with longer-term externalised harms to non-humans and the broader environment. This work explores further how the One Health Framework might be developed to remediate this deficiency, especially in the context of South Africa’s transformative constitutional legal framework, which requires positive action from the state to secure defined and often conflicting socio-economic and environmental outcomes.