Porto-spleno-mesenteric (PSM) venous thrombosis is a rare clinical condition that, while being mostly unrecognized, is nonetheless often severe with a high morbidity and mortality. PSM venous thrombosis is the cause of as many as 5-10% of all abdominal ischemic events, and it presents with a highly variable and non-specific pattern of abdominal symptoms. Such complex and non-specific presentation can delay diagnosis, determining the poor clinical outcome of this condition. This review article discusses the information available on the pathogenesis, clinical presentation, diagnosis and general management of PSM venous thrombosis, with a focus on a number of some clinical issues that remain unaddressed. In particular, the current understanding of the predisposing factors and the heterogeneous clinical manifestations of this condition are described in detail. The recent advances in imaging techniques, which are leading to an improved diagnostic accuracy and facilitate an early diagnosis are also presented. Further, the indications and limits of both pharmacological and surgical treatment options are discussed.