Details of the major pathways of metabolism have been elucidated, in large measure through work on experimental animals. It is unlikely that they differ qualitatively between mammalian species. The more important challenge facing researchers today is that of metabolic regulation, and of the integrated control of metabolic pathways in the whole organism. These aspects may well differ quantitatively or even qualitatively between species. In this review, methods for studying metabolism and metabolic regulation in humans are described. There are both scientific and practical advantages to performing studies of metabolic regulation in humans. The scientific advantages are clear from some fundamental differences in metabolic regulation between rats and humans, such as the importance of de novo lipogenesis to the deposition of body fat, and the metabolism of atherogenic triacylglycerol-rich lipoproteins. The practical advantages result mainly from the size of a human compared with that of most laboratory animals, enabling large blood samples to be obtained, and several measurement techniques to be applied at one time. Reasons for the persistence of animal experimentation as the norm, rather than the exception, among life science researchers are discussed.