However the fast and development in DNA sequencing and high throughput technology, most of the simple biological process even in prokaryotic cells are not fully understood. This is because genes, as well as their products (proteins), do not work independently they interact with each other and form a complicated network which is called the Gene Regulatory Networks (GRN). GRN help us to understand the disease ontology and to reduce the cost of drug development. Recently, researchers from Caltech are able to answer some of the difficult and ambiguous biological questions by unlocking the Secrets of the Gene Regulatory Networks. During the last decade, many GRN construction algorithms have been developed. In this book, we simplified GRN construction steps; enumerate some of important available tools, and discuses GRN challenges and future perspective.