Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with high morbidity and mortality in which long-term survival rates remain disastrous. Surgical resection is the only potentially curable treatment for early pancreatic cancer; however, the right patient qualification is crucial for optimizing treatment outcomes. With the rapid development of radiographic and surgical techniques, resectability decisions are made by a multidisciplinary team. Upfront surgery (Up-S) can improve the survival of patients with potentially resectable disease with the support of adjuvant therapy (AT). However, early recurrences are quite common due to the often-undetectable micrometastases occurring before surgery. Adopted by international consensus in 2017, the standardization of the definitions of resectable PDAC (R-PDAC) and borderline resectable PDAC (BR-PDAC) disease was necessary to enable accurate interpretation of study results and define which patients could benefit from neoadjuvant therapy (NAT). NAT is expected to improve the resection rate with a negative margin to provide significant local control and eliminate micrometastases to prolong survival. Providing information about optimal sequential multimodal NAT seems to be key for future studies. This article presents a multidisciplinary concept for the therapeutic management of patients with R-PDAC and BR-PDAC based on current knowledge and our own experience.