Biliary tract cancer (BTC) is a rare cancer with poor prognosis, characterized by considerable pathophysiological and molecular heterogeneity. While this makes it difficult to treat, it also provides targeted therapy opportunities. Current standard-of-care is chemotherapy ± immunotherapy, but several targeted agents have recently been approved. The current investigational landscape in BTC emphasizes the importance of biomarker testing at diagnosis. MDM2/MDMX are important negative regulators of the tumor suppressor p53 and provide an additional target in BTC (∼5–8% of tumors are MDM2-amplified). Brigimadlin (BI 907828) is a highly potent MDM2-p53 antagonist that has shown antitumor activity in preclinical studies and promising results in early clinical trials; enrollment is ongoing in a potential registrational trial for patients with BTC. Biliary tract cancer (BTC), an umbrella term for a number of tumor sub-types, is a rare cancer with a poor prognosis (5-year survival rate: 15% [1]). It is characterized by considerable pathophysiological and molecular heterogeneity, making it difficult to treat, but providing a number of potentially targetable genetic alterations. No targeted agents are approved in the first-line setting for patients with BTC; chemotherapy-based regimens with or without immunotherapy are the standard of care. Clinical trials into alternative immunochemotherapy regimens and FGFR2 inhibitors are ongoing, which may impact on first-line treatment options in the future. Second-line treatment options are largely chemotherapy-based for patients without targetable mutations, or targeted agents against FGFR2, IDH1, HER2, BRAF V600E, NTRK, DNA damage repair genes, KRAS and RET aberrations, some of which are investigational. MDM2 is an endogenous negative regulator of p53, hence aberrations of the MDM2 gene can result in inappropriate silencing of wild-type p53, potentially leading to tumorigenesis. MDM2 amplification is observed in ∼5–8% of BTCs; TP53 mutations are largely mutually exclusive. MDM2–p53 antagonists are in clinical development for the treatment of various hematologic and solid tumors. Brigimadlin, an MDM2–p53 antagonist currently in development in patients with BTC, has shown durable responses and no unexpected toxicities across two phase Ia/Ib studies in patients with solid tumors, including a number of patients with BTC. Comprehensive molecular testing is a key recommended in treatment guidelines for BTC. A PDF version of this infographic is available as supplemental material.