Treatment options depend on the extent of disease at presentation. While those with resectable tumors at presentation have traditionally undergone surgery first, a paradigm shift is moving toward neoadjuvant chemotherapy first with emerging evidence in favor of total neoadjuvant treatment (chemotherapy followed by chemoradiation). Surgical options now include both minimally invasive approaches in select centers where experience has accumulated. Those with borderline resectable disease will benefit from neoadjuvant chemotherapy and chemoradiation. Provided a favorable response, these patients can undergo surgery although a more extensive resection to include vascular structures is often necessary to achieve an R0 resection. Patients with locally advanced or metastatic disease on presentation should undergo definitive chemotherapy with FOLFIRINOX, gem-nabP or gemcitabine + capecitabine +/- radiation. If patients respond to a sufficient degree, resection can be considered. For those with distant metastases, intra-abdominal metastases should generally not undergo resection unless in a trial setting while metachronous isolated lung metastases can be resected with favorable outcomes. For PDAC patients with isolated liver metastases, hepatic artery infusion pump is currently under investigation. Targeted therapeutics in PDAC are under investigation with the help of next-generation sequencing that allows genomic mapping of tumor cells for the identification of treatment targets. Currently, PARP inhibitors are utilized for tumors with DDR deficiency, agents targeting certain KRAS mutations have been shown to be efficacious in select patients as well as TRK inhibitors. Immunotherapy is currently utilized in the small cohort of PDAC patients with dMMR and/or high microsatellite instability (MSI-H) and multiple studies are ongoing on combination immuno- and chemotherapy.