While the morphology and function of most of the cells of the exocrine and endocrine pancreas have been well described over several centuries, one important cell type in the gland, the pancreatic stellate cell (PSC), was first described only as recently as 30 years ago. Furthermore, it was to be another 16 years before the biology of these cells could begin to be studied because it was only in 1998 that methods were developed to isolate and culture PSCs from rodent and human pancreas. PSCs are now known to be key players in pancreatic fibrosis, a predominant histological feature of two major diseases of the pancreas – chronic pancreatitis and pancreatic cancer. In health, PSCs are in their quiescent phase and are characterised by abundant vitamin A storing lipid droplets in their cytoplasm. The cells are responsible for maintaining normal pancreatic architecture via regulation of the synthesis and degradation of extracellular matrix (ECM) proteins. Recently, PSCs have also been implicated in other functions as progenitor/stem cells, as immune cells and as intermediaries in exocrine pancreatic secretion in humans. During pancreatic injury, PSCs change to an activated, myofibroblast-like phenotype, characterised by loss of the vitamin A stores and the synthesis of excessive amounts of ECM proteins resulting in the fibrosis of chronic pancreatitis and pancreatic cancer. An ever increasing number of factors that stimulate and/or inhibit PSC activation via paracrine and autocrine pathways are being identified. Furthermore, the signalling pathways and second messengers mediating the effects of exogenous or endogenous factors on PSC function are being increasingly characterized. Importantly, it has now been clearly demonstrated, using both in vitro and in vivo approaches, that PSCs interact closely with pancreatic cancer cells to promote local tumour growth as well as distant metastasis. PSCs from primary tumours in the pancreas have also been shown to travel to distant metastatic sites where they likely facilitate the seeding and subsequent proliferation of cancer cells. In view of the central role of PSCs in both chronic pancreatitis and pancreatic cancer, current research is focussed on novel therapeutic strategies to inhibit/retard PSC activation and to interrupt their interaction with cancer cells so as alleviate chronic pancreatitis and/or inhibit tumour growth. The challenge that remains is to translate these pre-clinical developments into clinically applicable treatments for patients with chronic pancreatitis and pancreatic cancer.