Biologics have greatly improved the management of rheumatoid arthritis (RA), demonstrating efficacy and safety in alleviating symptoms, inhibiting bone erosion, and preventing loss of function. Unmet therapeutic needs in RA remain; however, further advances require an understanding of issues left unaddressed under the current treatment paradigm. Most biologic-na?ve and biologic-pretreated patients who initiate a biologic therapy, for example, do not reach American College of Rheumatology 50% (ACR50) response, and few achieve remission. Responses are often not durable, prompting frequent treatment switching. Predictive markers are unavailable to guide therapy selection, and clinical trial data are lacking on whether a tumor necrosis factor inhibitor (TNFi) is the best first-line biologic and on the optimal sequence of use for the different biologics. Risk of serious infection is the major safety concern. Translating preclinical and clinical findings into new therapeutics may help address unmet needs. An increasing body of evidence indicates that the cytokine interleukin (IL)-17A represents an important therapeutic target; ongoing trials with IL-17A inhibitors will determine whether these agents can address some of the unmet needs associated with current biologics.