Sinusoidal obstruction syndrome (SOS), formerly named venoocclusive disease, is a well-known complication of hematopoietic stem cell transplantation and ingestion of food or drinks contaminated by pyrrolizidine alkaloids. Many other drugs and toxins have been associated with SOS, including several chemotherapeutic agents and immunosuppressors. SOS contributes to significant morbidity and mortality in all these settings. This review describes the histologic lesions of SOS, details its pathogenesis as it is understood today, specifies the recent data on its causes and how it may influence clinical management of colorectal liver metastases, and discusses the current knowledge on diagnosis and preventive options.