As our understanding of the pathogenesis of autoimmune diseases is growing, new therapies are being developed to target disease-specific pathways. Since the introduction of etanercept in 1998, several biotechnological agents have been developed, most of them indicated in the treatment of rheumatoid arthritis, but also psoriatic arthritis. Most currently available molecules target TNF-alfa with different strategies (i.e., etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol), IL-6 (tocilizumab), CTLA-4 (abatacept), and B cells (rituximab, belimumab) as they are key mediators in the cascade of inflammation. Further, small molecules have been recently developed to target intracellular signaling, such as Janus Kinases for tofacitinib, the first FDA-approved small molecule for rheumatoid arthritis. Most novel treatments are being developed for arthritis with specific differences between rheumatoid and psoriatic arthritis, as well as for systemic lupus erythematosus, following the approval of belimumab. Finally, biologic therapies are effective also in gout, mainly targeting interleukin-1 to block the inflammasome. This review article describes the new and upcoming treatment options for rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, and gout to dissect what we should be aware of when discussing these new and promising molecules.