Chronic pancreatitis is a common disorder of which the underlying pathogenic mechanisms still are incompletely understood. In the last decade, increasing evidence has shown that activated pancreatic stellate cells play a key role in the fibrosis development associated with chronic pancreatitis as well as pancreatic cancer. During pancreatic injury or inflammation, quiescent stellate cells undergo a phenotypic transformation, characterized by smooth muscle α-actin expression and increased synthesis of extracellular matrix proteins. Hitherto, specific therapies to prevent or reverse pancreatic fibrosis are unavailable. This review addresses current insights into pathological mechanisms underlying chronic pancreatitis and their applicability as concerns the development of potential future therapeutic approaches.