Matrix metalloproteinases (MMP) comprise a family of structurally related proteinases that are believed to play a critical role in many physiological and pathological processes. Transgenic technology offers the possibility of determining whether MMPs contribute directly to these processes. For example, gain of function and loss of function models have confirmed causative roles of MMPs in the development of pulmonary emphysema and unexpectedly uncovered an MMP-dependent mechanism of inflammatory cell recruitment. Limitations of these techniques and powerful applications on the horizon are also presented as we embark on an era where controlled experiments can be performed in complex mammalian models.