The field of metabolism research has made a dramatic resurgence in recent years, fueled by a newfound appreciation of the interactions between metabolites and phenotype. Metabolic substrates and their products can be biomarkers of a wide range of pathologies, including cancer, but our understanding of their in vivo interactions and pathways has been hindered by the robustness of noninvasive imaging approaches. The past 3 decades have been flushed with the development of new techniques for the study of metabolism in vivo. These methods include nuclear-based, predominantly positron emission tomography and magnetic resonance imaging, many of which have been translated to the clinic. The purpose of this review was to introduce both long-standing imaging strategies as well as novel approaches to the study of perturbed metabolic pathways in the setting of carcinogenesis. This will involve descriptions of nuclear probes labeled with C and F as well C for study using hyperpolarized magnetic resonance imaging. Highlighting both advantages and disadvantages of each approach, the aim of this summary was to provide the reader with a framework for interrogation of metabolic aberrations in their system of interest.