Aberrant expression of the nitric oxide synthases (NOS) is frequently found in cancer. Nitric oxide (NO) can have both antitumor and pro-tumor effects, depending on its cellular source, and concentration. Predominantly tumor epithelial derived NO promotes proliferation, angiogenesis, and metastasis. Recent advances focus on identifying signal transduction networks involved in NO signaling, impact on epigenetic regulation, regulation of cancer stem cells and inflammation mediated carcinogenesis. The impact of NO on non-epithelial cell within tumors is more varied. NO signaling regulates the pro-tumorigenic immunosuppressive effects of myeloid derived suppressor cells and mesenchymal stromal cells, while NO has anti-tumorigenic effects when derived from M1-polarized macrophages and specific T cell subsets. These findings highlight the complexity of NO/NOS in tumor carcinogenesis and progression.