Technical Abstract: The Factor Separation Method (FacSep) is a modeling application that has been utilized in the study of biophysical responses to changes in the environment to assess the relative contribution of different atmospheric factors on a biological system. In this chapter we will discuss crop simulation and land surface model-based assessments of the sensitivity to past and future changes in climatic conditions: increasing carbon dioxide, soil moisture, temperature and radiative conditions, and crop management procedures (irrigation). FacSep is applied to discern specific contributions to plant responses by single variables or combinations of environmental conditions. Our FacSep analysis has shown that it is important to understand that biological responses are inherently dependent on multiple variables in the natural world and should not be limited to assessments of single specific parameters.