Cardiovascular disease remains a key issue in healthcare. During the last decade, transgenic and gene-targeted mouse technology has provided invaluable insights into cardiovascular molecular biology. Given the similarities between the mouse and human genomes, this study proposes that information experimentally derived using genetically manipulated mice can contribute significantly to the understanding of human cardiovascular pathophysiology. We first introduced the basic principles and methods of genetic manipulation, such as the breeding background in mice and the factors of construct design. Secondly, we reviewed the analyses related to genetic manipulation of the cardiovascular system from embryonic to adult mice. In conclusion, the gene-engineered mouse model is one of the most important tools developed in recent basic and clinical research.