"Spectrum holes" represent the potential opportunities for non-interfering (safe) use of spectrum and can be considered as multidimensional regions within frequency, time, and space. The core challenge for secondary radio systems is to be able to robustly sense when they are within such a spectrum hole. To allow a unified discussion of the core issues in spectrum sensing, the "Weighted Probability of Area Recovered (WPAR)" metric is introduced to measure the performance of a sensing strategy and the "Fear of Harmful Interference" FHI metric is introduced to measure its safety. These new metrics explicitly consider the impact of asymmetric uncertainties (and misaligned incentives) in the system model. Furthermore, they allow a meaningful comparison of diverse approaches to spectrum sensing unlike the traditional triad of sensitivity, probability of false-alarm, and probability of missed detection. These new metrics are used to show that fading uncertainty forces the WPAR performance of single-radio sensing algorithms to be very low for small values of FHI, even for ideal detectors. Cooperative sensing algorithms enable a much higher WPAR, but only if users are guaranteed to experience independent fading. Finally, in-the-field calibration for wideband (but uncertain) environment variables (e.g. interference and shadowing) can robustly guarantee safety (low FHI) even in the face of potentially correlated users without sacrificing WPAR.