The ability of the myocardium to successfully adapt to cardiac injury ultimately determines whether the heart will decompensate and fail, or whether instead it will maintain preserved function. Despite the importance of the myocardial response to cardiac injury, very little is known with respect to the biochemical mechanisms that are responsible for mediating and integrating the stress response in the heart. In the present review we will summarize recent experimental material which suggests that the heart possess a germ-line encoded "innate" stress response that is activated in response to diverse forms of tissue injury. The extant literature suggests that this innate stress response plays an important role in initiating and integrating homeostatic responses within the heart. Nonetheless, as will be discussed further herein, these inflammatory mediators all have the potential to produce cardiac decompensation when expressed at sufficiently high concentrations.