All cells rely on a complex interplay of both extracellular and intracellular signals to control their metabolism, growth and differentiation. Recent evidence shows that several free radicals and their derivatives are able to act as signalling molecules. However, these molecules are inherently reactive towards biological materials such as proteins, lipids and DNA. In fact, the destructive power of these compounds appears to be harnessed and used by organisms to destroy both invading pathogens and tumour cells. Therefore, their use as signals seems to be a puzzle. Here, their production, role in signalling, and involvement in some diseases are discussed.