The study of oxidative stress is a relatively young field of research in ruminant medicine. Oxidative stress results from increased exposure to or production of oxidants, or from decreased dietary intake, de novo synthesis or increased turnover of antioxidants. The understanding of the role of oxidants and antioxidants in physiological and pathological conditions is rapidly increasing. Oxidative stress is an active field of research in veterinary medicine and has been implicated in numerous disease processes including sepsis, mastitis, acidosis, ketosis, enteritis, pneumonia, respiratory, and joint diseases. Compared to human medicine, only a limited number of conditions have been investigated in regard to the effects of oxidative stress in ruminants. Studies in cattle have been sporadic and mainly with mastitis, pneumonia, and retained placenta. More recently, studies have been focused on metabolic diseases that affect dairy cows during the peripartum period. Numerous and rapidly evolving methodologies for evaluating oxidative stress are available to researchers and clinicians, each with their own distinct advantages and disadvantages. Differences in models and methodologies make it difficult to make meaningful comparisons, even for studies that seem quite similar superficially. With this in mind, it is the goal of this review to discuss the advantages and shortfalls of different methodologies commonly used to measure oxidative stress and damage in ruminants. Clarity of understanding of the pathophysiology of oxidative stress in ruminants will allow the design of specific antioxidant therapies. Future research should focus on the establishment of a reference panel of biomarker of oxidative stress to be used in ruminant medicine. To help accelerate practical applications, we propose the development of an oxidative stress index as an approach in ruminant and veterinary medicine.