What a relief! In 1955 the principle of strain release was put forward to explain the differing reactivity of axial and equitorial alcohols during oxidation. Our findings suggest that this same rationale may account for the differing rates of activation between axial and equitorial C–H bonds in C–H activation processes. In conjunction with steric and electronic considerations, strain-release can be used to qualitatively predict relative rates and site specificity of C–H activation in complex settings.