Although the development and regulatory approval of the thrombopoietin receptor agonists revolutionized aspects of the immune thrombocytopenia (ITP) treatment landscape over the past two decades, there remain many areas of high unmet need. Therefore, a number of investigational and repurposed agents are currently undergoing clinical development in ITP. In a departure from historical trials, which largely focused on the indefinite treatment of persistent or chronic ITP, ongoing trials run the gamut of disease phases, and include novel agents being evaluated in early phases of the disease to attempt to modify the disease course. Many agents in development target disease pathophysiologic mechanisms not previously targeted by agents in current use, including platelet autoantibody recycling, B-cell maturation and differentiation, long-lived plasma cells, and the complement system, among others. These agents represent promising treatment options for patients with otherwise refractory disease or who are intolerant of currently available therapies. Additionally, with our increasing understanding of the diverse immune mechanisms at play in ITP, the expansion of the therapeutic armamentarium to include agents targeting diverse pathophysiologic mechanisms may allow a more personalized therapeutic selection in the future. This manuscript provides an up-to-date, in-depth overview of recently completed and ongoing clinical trials in ITP.