Network models have been used to study the underlying processes and principles of biological systems for decades, providing many insights into the complexity of life. Biological systems require a constant flow of free energy to drive these processes that operate away from thermodynamic equilibrium. With the advent of high-throughput omics technologies, more and more thermodynamic knowledge about the biological components, processes and their interactions are surfacing that we can integrate using large-scale biological network models. This allows us to ask many fundamental questions about these networks, such as, how far away from equilibrium must the reactions in a network be displaced in order to allow growth, or what are the possible thermodynamic objectives of the cell.