In the present narrative review, we will illustrate the fascinating journey of this exercise-mimetic hormone across several stations, leading us to different territories, such as obesity, energy metabolism, adipogenesis and metabolic syndrome, muscle pathology, cardiovascular disease, and age-associated diseases (e.g., osteoporosis and osteoarthritis), finally landing at the neuroprotective role of irisin in age-associated dementia. Here, FNDC5 is linked to osteoporosis.