Toll-like receptors (TLRs) have been identified as primary innate immune receptors. They distinguish among different patterns of pathogens and rapidly activate an innate immune response. However, TLRs can also be stimulated by host-derived molecules. TLRs are expressed in the cardiovascular system and could thus be a key link between cardiovascular diseases and the immune system. Increasing evidence suggests that TLR signaling promotes injury in the heart after ischemia, ischemia/reperfusion or hypertrophic stimuli. Herein we review the experimental and clinical evidence for the involvement of TLR and its downstream signaling molecules in cardiac ischemic injury.