The major issue is that the LQ formula describes a continuously bending dose-response curve (the βD² component) whereas what is most commonly observed is a simple exponential response following an initial shouldered region. Thus using Eq. (2.2) to predict the BED of an SRS /SBRT treatment will potentially overestimate toxicity. A number of models have been proposed that counter this discrepancy. Of the many published models, the Universal Survival Curve (USC) of Park et al. offers a direct approach and grafts a multitarget dose-response model on to a standard LQ equation (Park et al. 2008). This has the benefit of better representing the biological reality of radiation lethality of simple survival curves, but does not address the many differences in clinical responses linked to SRS/SBRT that are discussed above. Many in the field are still divided on the issue, some suggesting that the LQ relationship is still valid, and others being less convinced (Park et al. 2008; Guerrero and Li 2004; Shibamoto et al. 2012). Sample calculations made using Eq. (2.2) illustrate the dramatic differences in calculated BED using the LQ formula for SRS/SBRT (Table 2.2). We would offer the following guidance: To generate an indication of the potency of a SRS/SRBT schedule compared to a conventional fractionation scheme, the LQ formula will provide appropriate estimates up to fractional doses in the range of 6–10 Gy. Above this, application of the LQ methodology will have reduced power to provide a comparison with conventional schedules. However, as in all applications of BED calculations, the result generated should only be considered as a guide. In the case of clinical questions related to normal tissue toxicity from SRS/SBRT schedules, empirically established dose limits and tolerances from relevant clinical literature should be respected for this increasingly used modality.