Tissue or organ regeneration is a complex process with successful outcomes depending on the type of tissue and organism. Upon damage, mammals can only efficiently restore a few tissues including the liver, skin, epithelia of the lung, kidney, and gut. In contrast, lower vertebrates such as zebrafish possess an extraordinary regeneration ability, which restores the normal function of a broad spectrum of tissues including heart, fin, brain, spinal cord, and retina. This regeneration process is either mediated by the proliferation of resident stem cells, or cells that dedifferentiate into a stem cell-like. In recent years, evidence has suggested that the innate immune system can modulate stem cell activity to initiate the regenerative response to damage. This review will explore some of the newer concepts of inflammation in zebrafish regeneration in different tissues. Understanding how inflammation regulates regeneration in zebrafish would provide important clues to improve the therapeutic strategies for repairing injured mammalian tissues that do not have an inherent regenerative capacity.