During the last two decades, clinical use of novel biological therapy has led to increased mechanistic understanding of complex rheumatological diseases. Conversely, basic and translational studies have led to development of new and varied therapeutic agents. These new medications which "target" specific steps in one or more immune pathways have the potential to control disease symptoms, improve quality of life and long-term prognosis, and perhaps in some, restore immunological tolerance. Use of these agents in clinical trials, combined with post-marketing surveillance, has revealed both the benefits and the undesirable side-effects of biological disease-modifying anti-rheumatic drugs (DMARDs). In this review we focus on the use of tocilizumab, a monoclonal antibody directed against the IL6 receptor (IL6R), which potently inhibits IL-6/IL6R signaling.