Pancreatic adenocarcinoma is a leading cause of cancer-related deaths in the United States, with incidence rates increasing from 1999 to 2008. High-quality multiphase imaging is crucial for distinguishing between curatively resectable and unresectable disease. Systemic therapy is used in neoadjuvant, adjuvant, locally advanced, and metastatic settings. Clinical trials are essential for advancing treatment options. The NCCN Guidelines for Pancreatic Adenocarcinoma focus on diagnosis, treatment with systemic therapy, radiation therapy, and surgical resection. Imaging, particularly multidetector CT angiography, is the primary modality for staging, with MRI and endoscopic ultrasound (EUS) providing complementary information. Biopsy is necessary before neoadjuvant therapy and for patients with locally advanced or metastatic disease. Biomarkers like CA 19-9 are useful for staging and surveillance. Gemcitabine monotherapy is recommended for frontline treatment in metastatic or locally advanced disease with good performance status. FOLFIRINOX is a preferred regimen for first-line treatment in metastatic disease. Second-line therapy options include fluoropyrimidine-based regimens and gemcitabine combinations. ChemoRT is generally used concurrently with gemcitabine- or fluoropyrimidine-based chemotherapy, with capecitabine-based chemoRT showing potential advantages in locally advanced disease.Pancreatic adenocarcinoma is a leading cause of cancer-related deaths in the United States, with incidence rates increasing from 1999 to 2008. High-quality multiphase imaging is crucial for distinguishing between curatively resectable and unresectable disease. Systemic therapy is used in neoadjuvant, adjuvant, locally advanced, and metastatic settings. Clinical trials are essential for advancing treatment options. The NCCN Guidelines for Pancreatic Adenocarcinoma focus on diagnosis, treatment with systemic therapy, radiation therapy, and surgical resection. Imaging, particularly multidetector CT angiography, is the primary modality for staging, with MRI and endoscopic ultrasound (EUS) providing complementary information. Biopsy is necessary before neoadjuvant therapy and for patients with locally advanced or metastatic disease. Biomarkers like CA 19-9 are useful for staging and surveillance. Gemcitabine monotherapy is recommended for frontline treatment in metastatic or locally advanced disease with good performance status. FOLFIRINOX is a preferred regimen for first-line treatment in metastatic disease. Second-line therapy options include fluoropyrimidine-based regimens and gemcitabine combinations. ChemoRT is generally used concurrently with gemcitabine- or fluoropyrimidine-based chemotherapy, with capecitabine-based chemoRT showing potential advantages in locally advanced disease.