Basic cancer research has mainly focused on mutations in cancer cells that result in either gain-of-function in oncogenes or loss-of-function in tumour-suppressor genes 1 . However, the EXTRACELLULAR MATRIX (ECM) of tumours and the non-cancerous, stromal cells within tumours also have an important impact on tumour progression 2 . Matrix metalloproteinases (MMPs) can regulate the tumour microenvironment, and their expression and activation is increased in almost all human cancers compared with normal tissue.MMPs are proteolytic enzymes and their basic mechanism of action -degradation of proteins -regulates various cell behaviours with relevance for cancer biology. These include cancer-cell growth, differentiation, apoptosis, migration and invasion, and the regulation of tumour angiogenesis and immune surveillance.Pharmaceutical inhibitors of MMPs have been developed, but the results from CLINICAL TRIALS with these drugs have proved disappointing. However, these first clinical trials were designed on the basis that MMPs were important for the late steps of tumour progression -that is, invasion and metastasis. With the current understanding of the diverse role of MMPs -particularly their relevance for the early steps in cancer progression, such as angiogenesis -these disappointing results seem less surprising. To better target MMPs for cancer treatment, an appreciation of their many functions -often acting in opposing directions in cancer progression -is needed.