Rheumatoid arthritis (RA) more and more becomes a syndrome, rather than a disease, with genetic, hormonal and environmental influences, among which smoking and the microbiota generate focused interest. The shared epitope and PTPN22 loci are associated with RA, and, particularly, with the "classical" form with anti-citrullinated peptide antibodies (ACPA) and IgM-rheumatoid factor (IgM-RF) positivity. Pregnancy is associated with a--temporary--remission of RA. Epidemiological studies have shown that oral contraception, parity and hormonal replacement therapy influence the severity of RA, and, this is still discussed, its incidence. Smoking is the first environmental factor strongly associated with RA, specifically with the shared epitope and with ACPA. The study of the microbiota is a novel emerging field that will help us to better understand patterns and evolution of RA.