In the last few years a number of methods have been developed that, in combination with the PCR method (1), have vastly improved the detection of mutations and polymorphisms. The most frequently used screening methods for mutation hunting in bleeding disorders are denaturing gradient gel electrophoresis (DGGE) (2), single-strand conformation polymorphism (SSCP) (3), and chemical mismatch cleavage (4). This chapter gives an introduction to the theory and practice of DGGE that facilitates the establishment of this mutation screening method.