Veno-occlusive disease, also known as sinusoidal obstruction syndrome (VOD/SOS), is a potentially life-threatening complication of allogeneic or autologous hematopoietic stem cell transplantation (HSCT) most commonly associated with high-intensity chemotherapies. The development of VOD/SOS may be rapid and unpredictable, and the importance of identifying risk factors to facilitate prompt diagnosis and timely treatment has become increasingly recognized. The reporting of new retrospective study data for adults and children and the emergence of novel anticancer therapies that may increase the risk of VOD/SOD also necessitate updates on risk factors, as provided in this review. The latest studies reporting VOD/SOS risk factors support previously published data, although the importance of patient-related factors, such as acute kidney injury, increased international normalized ratio, female sex (in children), and platelet refractoriness, is given greater emphasis in the recent data. Non-transplantation-related chemotherapies associated with increased risk for VOD/SOS include oxaliplatin and 5-fluorouracil chemotherapies. The novel antibody drug conjugates gemtuzumab ozogamicin and inotuzumab ozogamicin are now reported in product labeling to pose risks for VOD/SOS based on clinical trial data; an expert consensus panel has issued recommendations for risk reduction measures with inotuzumab ozogamicin treatment, including VOD/SOS prophylaxis and limitation to ≤2 inotuzumab ozogamicin treatment cycles. A wide range of biomarkers, including genetic, hematologic, hepatic, and inflammatory factors, as well as novel diagnostic techniques such as thromboelastography and measures of liver stiffness, may further enhance future risk calculation for VOD/SOS, although none has been widely adopted. Continual monitoring for and recognition of VOD/SOS risk factors are essential for optimal management of this complication.