The fact that some kinesin-related proteins can destabilize microtubules is now a well-established fact. However, the contribution that these kinesins make to cellular function is just coming into focus. Key structural and kinetic studies on the mechanism of microtubule depolymerization by these kinesins have provided a framework for understanding their cellular regulation and function. Completion of some of the genome sequences and recent technological advances enabling the rapid depletion of cellular proteins in metazoans have clarified the functional role and level of cooperation between members of the depolymerizing kinesin families. Recent studies utilizing these technologies have revealed how these kinesins play an integral role in the mechanics of mitotic spindle assembly, chromosome segregation and the shaping of connections in the brain.