With an increasing need to screen large numbers of chemicals, computational so-called in silico methods have become of growing interest. In this chapter, in silico screening is extensively reviewed and discussed with respect to food safety. These methods are used in several fields of application, to assess properties of chemical substances such as pharmaceuticals, pesticides and industrial chemicals. Their use is more common for regulatory purposes in the USA, but recent European regulations promote their use also in Europe. The specific application to evaluate hormone-disruptive chemicals has produced a number of tools. Their use for assessing properties of chemicals in food has also been evaluated, and it may offer several advantages. There are limitations, however, and the clear identification of possibilities, uncertainty and different uses is necessary for the correct application of the in silico tools.