The integration of lipoprotein-related or apolipoprotein-targeted nanoparticles as pharmaceutical carriers opens new therapeutic and diagnostic avenues in nanomedicine. The concept is to exploit the intrinsic characteristics of lipoprotein particles as being the natural transporter of apolar lipids and fat in human circulation. Discrete lipoprotein assemblies and lipoprotein-based biomimetics offer a versatile nanoparticle platform that can be manipulated and tuned for specific medical applications. This article reviews the possibilities for constructing drug loaded, reconstituted or artificial lipoprotein particles. The advantages and limitations of lipoprotein-based delivery systems are critically evaluated and potential future challenges, especially concerning targeting specificity, concepts for lipoprotein rerouting and design of innovative lipoprotein mimetic particles using apolipoprotein sequences as targeting moieties are discussed. Finally, the review highlights potential medical applications for lipoprotein-based nanoparticle systems in the fields of cardiovascular research, cancer therapy, gene delivery and brain targeting focusing on representative examples from literature.