The ability to predict individual breeding values in natural populations with known pedigrees has provided a powerful tool to separate phenotypic values into their genetic and environmental components in a nonexperimental setting. This has allowed sophisticated analyses of selection, as well as powerful tests of evolutionary change and differentiation. To date, there has, however, been no evaluation of the reliability or potential limitations of the approach. In this article, I address these gaps. In particular, I emphasize the differences between true and predicted breeding values (PBVs), which as yet have largely been ignored. These differences do, however, have important implications for the interpretation of, firstly, the relationship between PBVs and fitness, and secondly, patterns in PBVs over time. I subsequently present guidelines I believe to be essential in the formulation of the questions addressed in studies using PBVs, and I discuss possibilities for future research.