All organisms living in complex environments have evolved effective mechanisms of dynamic responses to extracellular stimuli. The immune system activates when damaged or injured cells release damage-associated molecular patterns (DAMPs). In addition to well-characterized DAMPs such as high-mobility group box 1 and adenosine triphosphate, studies on new classes of DAMPs have emerged. Here, we review recent reports of a new class of isoprenoid-derived DAMPs, including farnesyl pyrophosphate and geranylgeranyl pyrophosphate, both of which are pivotal metabolic intermediates of the mevalonate pathway. We also explore the roles of old and new DAMPs in autoimmune diseases that result from dysregulated inflammation. The findings highlight that understanding the functional mechanisms of DAMPs is important to enrich the DAMP family and decipher their immunoregulatory mechanisms to provide new therapeutics for the prevention and treatment of autoimmune diseases.