Over the past decade, our program has focused on understanding the role of the physiological environment, tumor vasculature, and metabolism in several of the aggressive phenotypic traits of cancer, such as invasion and metastasis. These studies have been performed primarily with magnetic resonance (MR) imaging (MRI) and spectroscopy (MRS) on human breast and prostate cancer models. During the course of these studies, we observed specific changes in choline phospholipid metabolism associated with a more aggressive phenotype. Molecular or pharmacologic interventions that reduced this aggressiveness were also consistent with a reversal of these alterations. In this contextual review, we have outlined the insight we have gained from these studies and have discussed some of the enzymes and pathways that may present novel targets for pharmaceutical interventions in cancer.