Microsatellite DNA loci have recently been adopted for many biological applications. Comparative studies across a wide range of species has revealed many details of their mutational properties and evolutionary life cycles. Experience shows that a full understanding of these processes is essential to ensure the effective use of microsatellites as analytical tools. In this article, we review the controversies that have arisen as biologists have taken up this new technology and the emerging consensus that has resulted from their debates. We point to the need for comparative DNA sequencing studies to produce input data for a new generation of theoretical models of microsatellite behaviour. We conclude by presenting our own conceptual model, ‘Snakes and Ladders’, as an aid to theory development.