Inflammation has been proposed as one of the hallmarks of cancer and therefore one of the main constituents of tumor development. Nitric oxide (NO) is a highly reactive molecule that exerts pleiotropic roles depending on the tissue type, dose, and duration of exposure. The role of NO in cancer progression is particularly controversial. While low-to-moderate doses have been shown to stimulate a more aggressive and invasive phenotype, high doses have been associated with induced cytotoxicity and cytostasis. In this review, we analyze the role of NO in different therapeutic approaches for breast and prostate cancers. In this regard, we discuss the results of different studies showing the efficiency of NO-donating drugs as a single-agent therapy inducing cytostasis, increased oxidative stress or autophagy-mediated cell death. NO has been widely studied not only as a sensitizer of the conventional chemotherapy strategies by reducing the hypoxia-mediated drug resistance or inhibiting commonly hyperactivated survival pathways in cancer as NK-kappa B but also as conjugated forms of chemotherapeutic agents that result in an increased efficacy and reduced toxicity. However, because of the pleiotropic effects, the effect of NO on cancer progression and its employment as a therapeutic target is still highly debated, and more preclinical and clinical studies are needed to clarify the role of NO in the different types and stages of cancer.