Small molecule drugs suffer from poor in vivo half-life, rapid degradation, and systemic off-target toxicity. To address these issues, researchers have developed nanoparticles that significantly enhance the delivery of many drugs while reducing their toxicity and improving targeting to specific organs. Recombinantly synthesized biomaterials such as elastin-like polypeptides (ELPs) have unique attributes that greatly facilitate the rational design of nanoparticles for drug delivery. These attributes include biocompatibility, precise control over amino acid sequence design, and stimuli-responsive self-assembly into nanostructures that can be loaded with a range of drugs to enhance their pharmacokinetics and pharmacodynamics, significantly improving their therapeutic efficacy over the free drugs. This review summarizes recent developments in genetically encoded, self-assembling ELP nanoparticles and their applications for drug delivery.