The existence of protective mechanisms in the adult brain is gradually being recognized as an important aspect of brain function. For many years, self-repair processes in the post-embryonic brain were considered of minor consequence or nonexistent. This notion dominated the study of neurotrophism. Thus, although the possibility that neurotrophic factors participate in brain function in adult life was prudently maintained, the majority of the studies on the role of trophic factors in the brain were focused on developmental aspects. With the recent recognition that the adult brain keeps a capacity for cell renewal, although limited, a new interest in the regenerative properties of brain tissue has emerged. New findings on the role of insulin-like growth factor I (IGF-I), a potent neurotrophic peptide present at high levels in serum, may illustrate this current trend. Circulating IGF-I is an important determinant of proper brain function in the adult. Its pleiotropic effects range from classical trophic actions on neurons such as housekeeping or anti-apoptotic/ pro-survival effects to modulation of brain-barrier permeability, neuronal excitability, or new neuron formation. More recent findings indicate that IGF-I participates in physiologically relevant neuroprotective mechanisms such as those triggered by physical exercise. The increasing number of neurotrophic features displayed by serum IGF-I reinforces the view of a physiological neuroprotective network formed by IGF-I, and possibly other still uncharacterized signals. Future studies with IGF-I, and hopefully other neurotrophic factors, will surely reveal and teach us how to potentiate the self-reparative properties of the adult brain.