Biologics have revolutionized the treatment of inflammatory joint disease in the last decade. By precisely targeting and inhibiting inflammatory cytokines as well as the blockade of cells centrally integrated in the immune system, inhibition of inflammation has become possible which had been unthinkable before. The medical need to improve our current approach with biologics even more is based on three observations: (1) even though the clinical effect of a given biologic is evident in the majority of patients, not all show a satisfactory response, (2) the blockade of important mediators of the immune system bears the risk of infection and potentially malignant events and (3) all current biologics need to be administered parenterally. The present review describes several innovative biologics and low molecular weight compounds which are currently being investigated in clinical trials in patients suffering from inflammatory rheumatic conditions. Some of them may become a part of our growing armamentarium to treat these diseases which still represent a major burden to the patients and society.