Hidradenitis suppurativa (HS) is a chronic, debilitating disease that is often recalcitrant to treatment, necessitating the use of increasingly efficacious agents. The FDA approval of biologic medications such as adalimumab, and more recently secukinumab and bimekizumab, for the treatment of moderate-to-severe HS has provided more targeted therapeutic options. However, many patients still have incomplete disease control with these medications or have contraindications to their use. Numerous other therapies, including TNF-alpha inhibitors, IL-17 inhibitors, IL-1 inhibitors, an IL-12/23 inhibitor, IL-36 inhibitors, JAK inhibitors, oral PDE-4 inhibitors, a CXC chemokine receptor inhibitor, an IRAK4 degrader, C5a inhibitors, tyrosine kinase inhibitors, and OX40 inhibitors, are being developed and/or undergoing investigation to further determine their efficacy and safety for this disease. Thus, this chapter summarizes both the on and off-label uses of several existing agents and describes the efficacy, safety, and application of multiple novel, pipeline therapies.