Living organisms have always had to cope with harsh environmental conditions and in order to survive, they have developed complex mechanisms to deal with them. These responses have been assembled in a concept called hormesis, which has been identified as an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to higher stress level. The main hormetic agents identified so far are irradiation, heat, heavy metals, antibiotics, ethanol, pro-oxidants, exercise and food restriction. The hormetic response involves the expression of genes that encode cytoprotective proteins such as chaperones like heat-shock proteins, antioxidant enzymes and growth factors. In this review we will discuss the hormetic response mainly during an oxidative challenge, and its relationship with senescence and aging, and some related diseases such as diabetes and neurodegeneration.