The reaction between nitrite and hemoglobin has been studied for over a century. However, recent evidence indicating nitrite is a latent vasodilatory agent that can be activated by its reaction with deoxyhemoglobin has led to renewed interest in this reaction. In this review we survey, in the context of our own recent studies, the chemical reactivity of nitrite with oxyhemoglobin, deoxyhemoglobin and methemoglobin, and place these reactions in both a physiological and pharmacological/therapeutic context.