Cellular metabolism is a defining feature in every physiologic and pathologic process. Through advances in metabolomics, systems biologists can now track the dynamic interactions of the metabolome with the epigenome, genome, transcriptome and proteome. Metabolomics as an analytical platform is still in its infancy, and the quality of data is highly dependent on sample preparation, including derivatization for gas chromatography coupled mass spectrometry (GCMS). Using a GCMS based approach, metabolism was found to play an important role in cellular proliferation, differentiation, apoptotic and autocrine signaling, and resistance to targeted cancer therapies. These results highlight how understanding cellular metabolism can provide important insights into cellular processes both in development and disease. Increased attention to how metabolism supports and regulates such diverse cellular responses will allow for more precise engineering of biological function and the identification of targeted therapies to cure disease.