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The aim of this review is to discuss the potential usefulness of novel advances in the class of biochemical markers, neo-epitopes. Neo-epitopes are post-translational modifications (PTMs) of proteins formed by processes such as protease cleavage, citrullination, nitrosylation, glycosylation and isomerization. Each modification results from a specific local physiological or pathobiologial process. Identification of each modification, and the affected tissue-specific protein, may produce a unique disease-specific biochemical marker. One example of neo-epitopes detectable in protein fragments are type II collagen degradation products. These 2nd generation biochemical markers have proven useful for research on joint damage. Such neo-epitopes are being utilized in translational medicine to estimate safety and efficacy in both preclinical models and clinical settings. More advanced, 3rd generation biochemical markers …