Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with premature mortality, severe morbidity, and functional impairment leading to considerable financial burden for both patients and society. Since disease progression and complications can differ from one patient to another, genetic markers are of potential relevance for identifying those individuals at a higher risk of more severe disease. RA is a complex polygenic disease. Cardiovascular (CV) disease due to accelerated atherogenesis is the most common cause of premature mortality in patients with RA. Several studies support the implication of genetic factors in the development of CV disease in RA. In addition to the strong association between alleles of the HLA-DRB1*04 shared epitope and both subclinical and clinically evident CV disease, genes implicated in inflammation and metabolism, such as TNFA, MTHFR, and CCR5, seem to be associated with a higher risk of CV disease in patients with RA. We propose the use of these genetic variants as molecular biomarkers that could help to predict disease outcome at diagnosis of RA and, therefore, to optimize the treatment and management of other risk factors from an early stage of the disease.