Regular exercise and physical activity are now considered lifestyle factors with positive effects on human health. Physical activity reduces disease burden, protects against the onset of pathologies, and improves the clinical course of disease. Unlike pharmacological therapies, the effects mediated by exercise are not limited to a specific target organ but act in multiple biological systems simultaneously. Despite the substantial health benefits of physical training, the precise molecular signaling processes that lead to structural and functional tissue adaptation remain largely unknown. Only recently, several bioactive molecules have been discovered that are produced following physical exercise. These molecules are collectively called "exerkines". Exerkines are released from various tissues in response to exercise, and play a crucial role in mediating the beneficial effects of exercise on the body. Major discoveries involving exerkines highlight their diverse functions and health implications, particularly in metabolic regulation, neuroprotection, and muscle adaptation. These molecules, including peptides, nucleic acids, lipids, and microRNAs, act through paracrine, endocrine, and autocrine pathways to exert their effects on various organs and tissues. Exerkines represent a complex network of signaling molecules that mediate the multiple benefits of exercise. Their roles in metabolic regulation, neuroprotection, and muscle adaptation highlight the importance of physical activity in maintaining health and preventing disease.