Natural, physiological processes in the body can act as barriers to effective nanoparticle delivery. In this seminar, I will discuss the unique advantages of small, organic micelles and their ability to harness such barriers for the detection and targeted delivery of therapeutics to diseases including cardiovascular and chronic kidney disease. For chronic kidney disease, while small molecule drugs have been proposed as a therapy to manage disease progression, repeated, high dosages are often required to achieve therapeutic efficacy, generating off-target side effects, some of which are lethal. To address these limitations, our lab has designed a kidney-targeting micelle (KM) platform toward drug delivery applications. Specifically, KMs were found to cross the glomerular filtration barrier and bind to specific surface markers present on renal tubule cells. In vivo, KMs were found to be biocompatible and showed higher accumulation in kidneys compared to nontargeted controls in vivo. We provide proof-of-concept studies for their utility in autosomal dominant polycystic kidney disease nanotherapy and their application using various routes of administration including oral and transdermal administration. We discuss the promise of nanomedicine, the tailored design necessary to match such promise, and their potential as next generation platforms for personalized medicine. Development of nanomicelles that can protect and deliver nucleic acid therapies to inhibit transformation into pathogenic cell types in cardiovascular disease will also be discussed.