The upper limit of vulnerability (ULV) is the weakest shock strength at or above which ventricular fibrillation (VF) is not induced when the shock is delivered during the vulnerable period. The ULV, a measurement made in regular rhythm, provides an estimate of the minimum shock strength required for reliable defibrillation that is as accurate or more accurate than the defibrillation threshold (DFT). The ULV hypothesis of defibrillation postulates a mechanistic relationship between the ULV—measured during regular rhythm—and the minimum shock strength that defibrillates reliably. Vulnerability testing can be applied at implantable cardioverter defibrillator (ICD) implant to confirm a clinically adequate defibrillation safety margin without inducing VF in 75%–95% of ICD recipients. Alternatively, the ULV provides an accurate patient-specific safety margin with a single fibrillation–defibrillation episode. Programming first ICD shocks based on patient-specific measurements of ULV rather than programming routinely to maximum output shortens charge time and may reduce the probability of syncope as ICDs age and charge times increase. Because the ULV is more reproducible than the DFT, it provides greater statistical power for clinical research with fewer episodes of VF. Limited evidence suggests that vulnerability testing is safer than conventional defibrillation testing.