The hypercoagulable state associated with malignancy is well described. However, the mechanisms by which tumors cause this hypercoagulable state are yet to be fully understood. This review summarizes the available literature of human and animal studies examining NETs and cancer-associated thrombosis. The methods for detecting and quantifying NET formation are growing but are not yet standardized in practice. Furthermore, it is important to distinguish between measuring neutrophil activation and NET formation, as the former can be present without the latter. Citrullination of histones by peptidylarginine deiminase 4 (PAD4) is considered one of the key pathways leading to NET formation. Cancer cells can prime neutrophils toward NET formation through the release of soluble mediators, such as interleukin-8, and activation of platelets, and may cause excess NET formation. Dismantling NETs through exogenous deoxyribonuclease has been shown to degrade NETs and reduce thrombus formation in vitro but may simultaneously release prothrombotic NET components, such as DNA and histones. Inhibiting PAD4 is far from clinical trials, but animal models show promising results with a potentially favorable safety profile. Interestingly, results from animal studies suggest that several therapies approved for other indications, such as interleukin-1 receptor blockade and JAK inhibition, may mitigate excessive NET formation or the prothrombotic effects of NETs in cancer. It is yet to be determined if inhibition of NET formation reduces cancer-associated thrombosis also in the clinical setting.