Abnormalities in liver enzymes are commonly encountered in clinical practice. Knowledgeable assessment requires a full understanding of their pathophysiology and provides an important means of detecting the earliest stage of many serious hepatobiliary disorders. The best interpretations are achieved using an integrated approach, combining historical and physical findings with routine and specialized diagnostic procedures and imaging studies. Information in this article provides the foundation, by example, for understanding the reliability of single time point enzyme measurements, the value of sequential measurements, the importance of interpreting the activity of enzymes in light of their half life and tissue of origin, and the influence of the induction phenomenon.