Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease that leads to inevitable joint destruction. The revised American College of Rheumatology (ACR) criteria for the diagnosis of RA are not sensitive enough for classification of the very early onset of the disease. They lack the predictive value for identifying patients at high risk of rapid joint damage and for assessing the efficacy of treatment. To improve the situation, several new biomarkers are currently studied to help to achieve this goal. Respecting the pathophysilogy of RA, several markers reflecting immune response, inflammation, joint destruction, and genetic factors are discussed in this review. Finally, the potential use of several markers in the clinical practice is depicted.