Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer-related mortality, largely due to a lack of highly safe and effective therapeutic options. A large proportion of the tumour's mass consists of a dense fibrous stroma, which could provide valuable therapeutic targets. This review elucidates the various possible stromal targets in PDAC, methods of targeting them and the outcomes of this targeting in in-vitro studies, studies on murine models of PDAC and clinical studies. While targeting some stromal components in PDAC yielded disappointing results in clinical studies, others have shown promise in multiple settings. More research efforts should be directed towards identifying additional stromal targets and evaluating their therapeutic potential. In addition, comprehensive clinical studies are essential to evaluate the safety and effectiveness of agents targeting stromal components of PDA of agents targeting stromal components of PDAC, both as monotherapies and in combination with standard surgical and pharmacological treatments for PDAC to improve patient’s outcomes.