It is clear that A Disintegrin And Metalloproteinase with ThromboSpondin motif (ADAMTS)-5 is the major aggrecanase in mouse cartilage, however it is not at all clear which enzyme is the major aggrecanase in human cartilage. Identifying the human aggrecanase is difficult because multiple, independent, molecular processes determine the final level of enzyme activity. As investigators, we have good methods for measuring changes in the expression of ADAMTS mRNA, and good methods for detecting aggrecanase activity, but no methods that distinguish the source of the activity. In between gene expression and enzyme action there are many processes that can potentially enhance or inhibit the final level of activity. In this editorial we discuss how each of these processes affects ADAMTS activity and argue that measuring any one process in isolation has little value in predicting overall ADAMTS activity in vivo.