Rheumatoid arthritis (RA) is an autoimmune disease of unknown cause and a chronic and progressive inflammatory disorder ensuing in genetically predisposed subjects, characterized by synovitis causing joint destruction, as well as inflammation in body organ systems, leading to anatomical alteration and functional disability. Immune competent cells, deregulated synoviocytes and cytokines play a key role in the pathophysiological mechanisms. The immune system function shows time-related variations related to the influence of the neuroendocrine system and driven by the circadian clock circuitry. Immune processes and symptom intensity in RA are characterized by oscillations during the day following a pattern of circadian rhythmicity. A cross-talk between inflammatory and circadian pathways is involved in RA pathogenesis and underlies the mutual actions of disruption of the circadian clock circuitry on immune system function as well as of inflammation on the function of the biological clock. Modulation of molecular processes and humoral factors mediating in RA the interplay between the biological clock and the immune response and underlying the rhythmic fluctuations of pathogenic processes and symptomatology could represent a promising therapeutic strategy in the future.