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Background: Pancreatic cancer (PDAC) – even if deemed resectable – has still a dismal prognosis and is the seventh leading cause of global cancer-related death with rising incidence worldwide. Summary: Surgical resection at best in combination with adjuvant systemic chemotherapy is the only potentially curative treatment. Surgical treatment has substantially improved over the last years with significantly reduced perioperative morbidity and mortality. Even when deemed radiologically resectable, the majority of PDAC is likely to have micrometastases, leaving most PDAC patients with an advanced stage. Recent 5-year overall survival was up to 46% in patients eligible for surgery with intensified adjuvant chemotherapy. Eligible for curative surgery are about one-third of the patients, and only 20% of these patients have the option for cure with surgery and adjuvant chemotherapy. Standards of care in treating PDAC patients include various mostly combinational chemotherapy approaches in the advanced and adjuvant setting. Moreover, first targeted therapies for individualizing treatment, e.g., specific subgroups like BRCA1/2 germline mutated patients, were established lately. Neoadjuvant concepts are currently part of research. This review focuses on current and future multimodal treatment options of PDAC and the impact of molecular profiling for individualizing treatment. Key Messages: State of the art in pancreatic cancer therapy is multimodal and includes novel strategies to allow molecular defined subgroup-specific treatment.