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The primary focus of this review is lipoprotein-based drug carriers, more specifically, high-density lipoprotein (HDL) type nanoparticles (NPs). These nanostructures are discussed regarding their suitability for clinical applications, particularly cancer therapy. Poor solubility and insufficient capability to selectively target malignant tumors represent significant challenges facing many anticancer drugs. Nevertheless, we and others have found that most, if not all, of these difficulties, can be overcome by incorporating drugs into lipoprotein nanocarriers (1). While not a novel approach, as HDL type NPs have been documented to deliver anticancer agents to cancer cells effectively and tumors (2-5), including those that, on their own (without facilitation), exhibited less than desirable therapeutic efficacy (6), due to their desirable features (see below), HDL type drug carriers, at least in our view, hold tremendous promise as facilitators of cancer chemotherapy. One of the key aspects of the HDL-type NP-facilitated drug transport is the receptor-mediated uptake of the payload from the NPs (7,8). Consequently, in this review, major emphasis is placed on monitoring the expression of the scavenger receptor type B1 (SR-B1) as a potentially valuable tool for the pre-treatment selection of patients regarding their suitability for advanced, personalized chemotherapy. The main emphasis in this article is on developing novel cancer therapeutics, while approaches for treating other diseases via lipoprotein nanocarriers are briefly discussed.