Although the lupus community has not witnessed the same growth in drug approvals as in inflammatory arthritis, there have been major breakthroughs since the mid-twentieth century. The discovery in the late 1940’s of cortisone revolutionised the treatment of patients not only with lupus but with all inflammatory diseases. During the 1950’s, azathioprine was introduced as a chemotherapeutic agent, but it was adopted soon thereafter as a drug for patients with rheumatic diseases. The antimalarial quinacrine was first used in the early 1950’s as well. The application of cyclophosphamide, the eighth cytotoxic anticancer drug approved by the FDA, to patients with severe forms of lupus continues to this day. One of the treatment highlights of the modern era came in the late part of the twentieth century with the approval of mycophenolate mofetil for acute kidney transplant rejection. Shortly thereafter in the early part of the twenty-first century, it was adopted as standard of care to rival cyclophosphamide for lupus nephritis, although not FDA-approved for this condition. Despite the outlook for the patient with lupus improving, the need for more efficacious and safer drugs was well recognised. The twentieth century closed with a foray into clinical trials, but the outcomes of these research efforts were unsuccessful until two positive phase 3 studies with belimumab led to its approval in 2011. Despite the path blazed during the belimumab development program, drug development research in lupus remains quite challenging. The obstacles to drug development are many and relate to the effectiveness of the drug, selection of the correct dose, inclusion of the proper patient population, and the incorporation of appropriate outcome measures, to name just a few. Despite these hurdles, there is currently unprecedented activity in the area of drug development in patients with lupus. The lupus community will overcome these barriers, and no doubt physicians will have more drugs in their armamentarium in the near future.