Metabolism plays a key role in many major human diseases. Generation of high-throughput omics data has ushered in a new era of systems biology. Genome-scale metabolic network reconstructions provide a platform to interpret omics data in a biochemically meaningful manner. The release of the global human metabolic network, Recon 1, in 2007 has enabled new systems biology approaches to study human physiology, pathology and pharmacology. There are currently more than 20 publications that utilize Recon 1, including studies of cancer, diabetes, host-pathogen interactions, heritable metabolic disorders and off-target drug binding effects. In this mini-review, we focus on the reconstruction of the global human metabolic network and four classes of its application. We show that computational simulations for numerous pathologies have yielded clinically relevant results, many corroborated by existing or newly generated experimental data.