The aim of this paper is to examine the features of “stealth” long circulating nanocarriers and the pharmacokinetic outcomes of stealthiness, and it will showcase the most investigated approaches yielding prolonged circulation of surface-engineered nanocarriers. These carriers are in the nanometer range size and most of them have been intended for the delivery of anticancer drugs to tissues affected by this pathology. Over the last decades, a number of different long circulating vehicles have been developed for theranostic purposes. Beside the development of new drugs with potent and selective activities, nanotechnology offers novel opportunities to cancer fighting by providing adequate tools for early detection and personalized treatments. Nevertheless, over the past few decades, significant advances have been made in fundamental cancer biology, allowing for remarkable improvements in diagnosis and therapy for cancer. Deaths caused by cancer are forecasted to rise to over 13.1 millions in 2030 (Globocan, 2008, IARC, 2010). About 70% of all cancer deaths occurred in low- and middle-income countries. In this paper, the basic concept underlining the “stealth” properties of drug nanocarriers, the parameters influencing the polymer coating performance in terms of opsonins/macrophages interaction with the colloid surface, the most commonly used materials for the coating process and the outcomes of this peculiar procedure are thoroughly discussed.Ĭancer is a leading cause of death worldwide as accounted for 7.6 million deaths (around 13% of all deaths) in 2008 (source: WHO Fact sheet N☂97 February 2012). In particular, stealth nanocarriers can be obtained by polymeric coating. In order to endow nanosystems with long circulation properties, new technologies aimed at the surface modification of their physicochemical features have been developed. Consequently, they are rapidly removed from the circulation mostly by the mononuclear phagocyte system. Nanocarriers interact massively with the surrounding environment, namely, endothelium vessels as well as cells and blood proteins. By virtue of their small size they can be injected intravenously and disposed into the target tissues where they release the drug. Many colloidal drug delivery systems are underdevelopment to ameliorate the site specificity of drug action and reduce the systemic side effects. Over the last few decades, nanocarriers for drug delivery have emerged as powerful tools with unquestionable potential to improve the therapeutic efficacy of anticancer drugs.