Chronic and acute pancreatitis can be understood as distinct stages of an inflammatory spectrum in the pancreas. Although its pathogenesis is not well defined, oxidative stress seems to be clearly involved in its development. During acute pancreatitis, there is an extraordinary and rapid formation of reactive oxygen species that leads to the extinction of pancreatic antioxidant reserves, causes direct tissue damage and activates oxidative cellular mediators, giving rise to the lesion. However, classical antioxidants have not been shown to have clear benefits in patients with acute pancreatitis. Chronic pancreatitis seems to be the result of a recurrent lesion and defective repair, leading to pancreatic atrophy and fibrosis. In this process, oxidative stress is an efficient stimulus to maintain pancreatic stellar cells active, the fibrogenic motor of chronic pancreatitis. Although antioxidant supplements relieve abdominal pain in these patients, the direction of future antioxidant therapies lies in identifying oxidative mechanisms with the potential for intervention.