In the World Anti-doping Agency 2008 Prohibited List, the prohibited substances of S2 item are hormones and related substances, which are belonging to the endogenous biomacromolecules. How to identify the substances derived from endogenous secretion or exogenous administration is the main problem in doping control analysis and attracts more attention. The present report summarizes the main analytical strategies, including indirect blood tests and direct detection approaches developed to identify the presence of erythropoietin (EPO) and human growth hormone (hGH), which have wide pharmaceutical applications and thus been fully examined. The recent physico-chemical or immunoanalytical methodologies on the discrimination of recombinant and endogenous proteins are emphasized.