Matrix metalloproteinases are a family of highly regulated peptidases that are collectively responsible for the degradation of extracellular matrix during tissue remodeling. Dysregulated activity has long been implicated in the pathologies of cancer and arthritis, and the number of diseases more recently associated with these enzymes has been increasing. In the past year, new transgenic models of matrix metalloproteinase knockouts have been described, allowing the direct assessment of specific enzyme activity in particular disease models. In addition, more selective inhibitors with improved pharmacokinetic profiles have entered clinical trials, allowing the assessment of the safety and efficacy of this strategy.