Pancreatic cancer has the highest mortality rate (5-year survival ~9%) among major types of malignant tumors. Pancreatic adenocarcinoma (PAAD) is the most common (>80%) and most lethal type of pancreatic cancer. A strong need thus exists for new approaches to treat PAAD. G protein-coupled receptors (GPCRs), the largest family of cell-surface receptors and drug targets, account for ~35% of approved drugs. Recent studies have revealed roles for GPCRs in PAAD cells and cells in the tumor microenvironment. This review assesses current information regarding GPCRs in PAAD by first summarizing omics data for GPCRs expression in PAAD. The PAAD “GPCRome” includes GPCRs with approved agents, thereby offering potential for their repurposing/repositioning. In addition, we review the evidence for functional roles of specific GPCRs in PAAD. We also highlight gaps in understanding the contribution of GPCRs to PAAD biology and identify several GPCRs that may be novel therapeutic targets so as to help guide future work in search of GPCR-targeted drugs to treat PAAD tumors.This article is protected by copyright. All rights reserved.