Considerable evidence exists for oxidative damage to extracellular materials during multiple human pathologies. Unlike cells, the extracellular compartment of most biological tissues is less well protected against oxidation than intracellular sites in terms of the presence of both antioxidants (low molecular mass and enzymatic) and repair enzymes. The extracellular compartment may therefore be subject to greater oxidative stress, marked alterations in redox balance and an accumulation of damage due to slow turnover and/or poor repair. The nature and consequences of damage to ECM (extracellular matrix) are poorly understood, despite the growing realization that changes in matrix structure not only have structural consequences, but also play a key role in the regulation of cellular adhesion, proliferation, migration and cell signalling. The ECM also plays a key role in cytokine and growth factor binding, and matrix modifications would therefore be expected to alter these parameters. In the present study, we review mechanisms of oxidative damage to ECM, resulting changes in matrix structure and how this affects cellular behaviour. The role of such damage in the development and progression of inflammatory diseases is also discussed with particular reference to cardiovascular disease.