Conformation sensitive gel electrophoresis (CSGE) is a rapid screening method for the detection of DNA sequence variation, specifically single-base changes or small insertions and deletions. It has been widely used for mutation screening in genetic disorders and for the detection of single nucleotide polymorphisms (SNPs).CSGE is a simple manual method, based on heteroduplex analysis, and compares well in terms of sensitivity with other screening technologies. CSGE also lends itself to automation and such modi-fications have been useful in increasing sample throughput and sensitivity. However, manual CSGE remains a low-cost, accessible, and effective approach for mutation screening, which can be carried out with -minimal specialist equipment. This chapter describes manual CSGE, and outlines some of the uses, -modifications, and limitations of this method.