Substitution lookups allow you to supply glyph substitutes. There are several types of glyph substitution. The most common one is the ligature substitution, but which ones you want to use depends on what you want to achieve.
Within the OpenType Designer you can add specific substitution lookups to your features.
Note: Even though the OpenType specification prohibits it, FontCreator allows you to define entries in a multiple substitution lookup with no output glyphs. This is a trick to delete glyphs, and seems to be supported by Windows and web browsers.