Inflammation is a formidable ally in the constant battle against infection, cancer and tissue injury. It is a primordial response that protects against injury and restores damaged tissue to its normal physiological functioning. In fact, our wellbeing and survival depends upon its efficiency and carefully balanced control. In general, the innate inflammatory response initiates within minutes and, if all is well, resolves within hours. In contrast, chronic inflammation persists for weeks, months or even years. Here, we are going to discuss the key endogenous checkpoints necessary for mounting an effective yet limited inflammatory response and the crucial biochemical pathways necessary to prevent its persistence. In this setting, the biochemical synthesis of key pro-resolution eicosanoids as well as their mode of action in self-limiting inflammation will be discussed.