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In 2010, the combination of cisplatin + gemcitabine (CISGEM) showed its superiority over gemcitabine alone in first-line treatment of advanced biliary tract cancers (BTCs) in the ABC-02 trial. For more than ten years now, no study has shown a benefit in intensifying chemotherapy or combining targeted therapy with CISGEM. Recently, a positive step has finally been taken, with the demonstration of the benefit provided by the addition of an immunotherapy to CISGEM, first durvalumab in the TOPAZ-1 study (the new first-line treatment standard), then pembrolizumab in the KEYNOTE-966 trial. BTCs contain frequent molecular alterations, whose therapeutic targeting has already been demonstrated to be effective in the second line or higher and could also be interesting in the first line in the future.