Several international organizations establish minimum safety standards to ensure that workers and the general population are protected against adverse health effects associated with electromagnetic radiation. Suitable standards are typically defined using published experimental data. To date, few experimental studies have been conducted at Terahertz (THz) frequencies, and as a result, current THz standards have been defined using extrapolated estimates from neighboring spectral regions. In this study, we used computational modeling and experimental approaches to determine tissue-damage thresholds at THz frequencies. For the computational modeling efforts, we used the Arrhenius damage integral to predict damage-thresholds. We determined thresholds experimentally for both long (minutes) and short (seconds) THz exposures. For the long exposure studies, we used an in-house molecular gas THz laser (υ= 1.89 THz, 189.92 mW/cm2, 10 minutes) and excised porcine skin. For the short exposure studies, we used the Free Electron Laser (FEL) at Jefferson Laboratory (υ= 0.1-1.0 THz, 2.0-14.0 mW/cm2, 2 seconds) and wet chamois cloths. Thresholds were determined using conventional damage score determination and probit analysis techniques, and tissue temperatures were measured using infrared thermographic techniques. We found that the FEL was ideal for tissue damage studies, while our in-house THz source was not suitable to determine tissue damage thresholds. Using experimental data, the tissue damage threshold (ED50) was determined to be 7.16 W/cm2. This value was in well agreement with that predicted using our computational models. We hope that knowledge of tissue-damage thresholds at THz frequencies helps to ensure the safe use of THz radiation.