Methods for the analysis of space-time clusters have been used frequently in epidemiology and public health in recent decades. However, they have generally been applied without an appropriate critique of their limits and usefulness. This article reviews some of the most important issues involved in improving the interpretability and utility of such methods in this context. We begin with a brief discussion about the epidemiological meaning of the concept of space-time clustering. We then describe five commonly used methods, including the procedures for their use. We also present a conceptual and statistical generalization of the techniques. Finally, we summarize some important issues for use of these methods in epidemiology and public health.