In the United States, colorectal cancer (CRC) is the third leading cause of cancer mortality, with limited treatment options for those with advanced disease. Matrix metalloproteinases (MMPs) are important for maintaining extracellular homeostasis but also play a prominent role in cancer cell invasion and dissemination. Expression levels of MMP-1, -2, -7, -9 and -13 correlate with worse outcomes; MMP-12 expression appears to be protective. Hence, MMPs are attractive therapeutic targets. Previous clinical trials using broad-spectrum MMP inhibitors were disappointing because of off-target toxicity and lack of efficacy. Now, the availability of safer, more selective inhibitors has renewed interest in therapeutic targeting of MMPs.