Research in designing and engineering long-circulating nanoparticles, so-called ‘stealth’ nanoparticles, has been attracting increasing interest as a new platform for targeted drug delivery, especially in chemotherapy. In particular, the modification of nanoparticulate surfaces with poly(ethylene glycol) derivatives has illustrated a decreased uptake of nanoparticles by mononuclear phagocyte system cells and, hence, an increased circulation time, allowing passive accumulation in the tumor. The clinical trials on patients with solid tumors are described in this article, to illustrate this generation of promising nanoparticles. In the last few years, the new-generation technique of grafting ligands on the nanoparticle surface in order to target and penetrate specific cancer cells has been developed. This article discusses the benefits of passive targeting for drug delivery to the solid tumors via the enhanced permeability and retention effect, when using stealth nanoparticles, and compares them with the advantages of active targeting.