The investigation of metabolic regulation at the transcriptional level presents different challenges than those encountered in the study of other important problems like development or cancer. Levels of key components like glucose, insulin, and lipids can be modulated but rarely change in an all-or-none fashion, necessitating quantitative techniques that can be applied to multiple tissues and systems. This review examines recent advances in methods for studying transcriptional regulation, with special emphasis on metabolic science. We compare these methods for investigators trying to decide on the best approach for their particular physiological paradigm or model system.