Purpose of Review <p>Current rheumatoid arthritis (RA) treatment guidelines recommend a treat-to-target approach with a goal of remission or low disease activity. Despite the wide variety of current molecular targets, many patients are difficult to treat and fail to respond. This review aims to highlight recent advances in precision medicine and novel therapeutic targets in RA, which may lead to better disease control or possibly cure in the future.</p> Recent Findings <p>Precision medicine is within its infancy in RA with recent and ongoing investigations into synovial phenotyping and metabolomics. Within the past several years, there have been investigations into multiple molecular pathways to treat rheumatoid arthritis. Multiple pathways targeting T-cells including PD-1, CD40-CD40L, OX40-OX40L, sphingosine-1-phosphate receptor-1, and C-X-C Chemokine Receptor Type 5 have been investigated in phase 1 and 2 trials. Recent advances in B-cell-directed therapy have included investigations into Bruton’s tyrosine kinase inhibitors and Anti-FcRn Monoclonal Antibodies. Novel cell types are also being evaluated with increased research on fibroblasts with both cyclin dependent kinase and interleukin-1-associated kinase 4 inhibitors modifying pathways within these cell types. Finally, there has been promising research utilizing CAR-T and bispecific antibodies that have the potential for a variety of downstream effects.</p> Summary <p>While rheumatoid arthritis is one of the most common diseases seen in a rheumatology office, there continues to be significant unmet needs. Within the last several years, a plethora of research has identified disease phenotypes and evaluated multiple novel therapeutic targets with mixed results. This review highlights many of the pathways under investigation. </p>