Recent technological advances have enabled comprehensive determination of the molecular composition of living cells‎.‎ The chemical interactions between many of these molecules are known‎,‎ giving rise to genome‎-scale reconstructed biochemical reaction networks underlying cellular functions‎.‎ Mathematical descriptions of the totality of these chemical interactions lead to genome‎-scale models that allow the computation of physiological functions‎.‎ Reflecting these recent developments‎,‎ this textbook explains how such quantitative and computable genotype‎-phenotype relationships are built using a genome‎-wide basis of information about the gene portfolio of a target organism‎.‎ It describes how biological knowledge is assembled to reconstruct biochemical reaction networks‎,‎ the formulation of computational models of biological functions‎,‎ and how these models can be used to address key biological questions and enable predictive biology‎.‎ Developed through extensive classroom use‎,‎ the book is designed to provide students with a solid conceptual framework and an invaluable set of modeling tools and computational approaches‎.‎