The main objective of this book is to discuss the statistical procedures used to evaluate DNA symmetry, also known as second Chargaff’s parity rule and its extension. The symmetry phenomenon is related with DNA word composition analysis. The analysis of DNA symmetry can contribute to predicting regulatory elements, functional elements, motifs, detect/predict patterns in genome sequences or evaluate the relationship between species. The biological hypotheses are tested by Monte Carlo procedures and a simulation model to address DNA symmetry phenomenon is proposed.