Abstract Treatment of primary biliary cholangitis (PBC) with ursodeoxycholic acid (UDCA) is not always sufficient to prevent progression to hepatic decompensation and/or need for liver transplant. Adjuvant therapy with obeticholic acid may provide additional biochemical improvements in some patients, but it is not well‐tolerated by patients with significant itch or advanced cirrhosis. Thus, new and creative approaches to treating patients with PBC are important to identify. This review discusses major potential therapeutic targets in PBC and provides examples of some specific agents currently in development for the treatment of PBC. Targets are broadly classified into those which strive to modify bile, inflammation, cell survival, or fibrosis. In bile, shrinking the size of the bile acid pool or modifying the quality of the bile by making it more hydrophilic or enriched in phosphatidylcholine may ameliorate cholestatic injury. Biliary epithelial cell survival may be extended by fortifying the bicarbonate umbrella or improving cell membrane integrity. Autoimmunity and cholangitis have the potential to be improved via regulation of the immune system. Targeting cytokines, immune checkpoints, and anti‐mitochondrial antibodies are examples of a more focused immunosuppression approach. Stem cell therapy and lymphocyte trafficking inhibition are more novel methods of broad immune regulation. Anti‐fibrotic therapies are also potentially useful for preventing progression of PBC. The nuclear hormone receptors, farnesoid X receptor (FXR) and peroxisome proliferator–activated receptor (PPAR) regulate many of these pathways: cholestasis, inflammation, and fibrosis, which is why they are being enthusiastically pursued as potential therapeutic targets in PBC.