There has been considerable controversy about methods for assessing life stress. However, self-report checklists and interview-based measures (the predominant approaches used in current research) differ in several respects, ranging from basic definitions through theoretical assumptions. Most research comparing these two approaches has focused on global comparisons in predicting disorder, which fail to take into account more specific information on how the methods vary. The present article outlines three stages of assessment for life stress: definition, operationalization, and quantification. Detailed examination of these stages with a sample of depressed patients helps to demonstrate in an explicit manner how self-report checklists and interview-based methods differ al successive stages of the measurement process. Data are presented that indicate large endpoint discrepancies attributable to specific differences in the definitional and operational procedures used in the two assessment approaches. The nature of the discrepancies found is discussed, along with the implications for assessing life stress and testing its implications for health and well-being.