Cell death and injury often lead to release or exposure of intracellular molecules called damage-associated molecular patterns (DAMPs) or cell death-associated molecules. These molecules are recognized by the innate immune system by pattern recognition receptors – the same receptors that detect pathogen-associated molecular patterns, thus revealing similarities between pathogen-induced and non-infectious inflammatory responses. Many DAMPs are derived from the plasma membrane, nucleus, endoplasmic reticulum and cytosol. Recently, mitochondria have emerged as other organelles that function as a source of DAMPs. Here, we highlight the significance of mitochondrial DAMPs and discuss their contribution to inflammation and development of human pathologies.