Long duration space missions present unique radiation protection challenges due to the complexity of the space radiation environment, which includes high charge and energy particles and other highly ionizing radiation such as neutrons. Based on a recommendation by the National Council on Radiation Protection and Measurements, a 3% lifetime risk of exposure-induced death for cancer has been used as a basis for risk limitation by the National Aeronautics and Space Administration (NASA) for low-Earth orbit missions. NASA has developed a risk-based approach to radiation exposure limits that accounts for individual factors (age, gender, and smoking history) and assesses the uncertainties in risk estimates. New radiation quality factors with associated probability distribution functions to represent the quality factor's uncertainty have been developed based on track structure models and recent radiobiology data for high charge and energy particles. The current radiation dose limits are reviewed for spaceflight and the various qualitative and quantitative uncertainties that impact the risk of exposure-induced death estimates using the NASA Space Cancer Risk (NSCR) model. NSCR estimates of the number of "safe days" in deep space to be within exposure limits and risk estimates for a Mars exploration mission are described.