Molecular and multimodal imaging procedures that complement the use of existing anatomical modalities for the diagnosis and monitoring of rheumatoid arthritis (RA) have undergone substantial developmental advances. These techniques have the potential to greatly improve the management of patients with RA through early diagnosis and maximization of the newly available opportunities for early therapeutic intervention. Quantitative, noninvasive monitoring of biomarkers of the molecular events induced during the onset of RA could be used to guide the initial selection of therapy and for assessment of early therapeutic responses. Biomolecular imaging techniques that can reveal the pathophysiological features of RA - including infrared thermography, near-infrared molecular imaging, and PET - are being used to investigate the earliest cellular and biochemical inflammatory events in the development of the disease. Noninvasive imaging of abnormal specific molecular events in early RA could enable early targeted intervention that could be tailored to optimize patient responses before destructive anatomical changes occur. In this Review, we summarize new advances in biomolecular imaging techniques, with an emphasis on their current state of development in terms of the management of RA. © 2012 Macmillan Publishers Limited.