Nanofluidic implantables represent a recent advance in a broad effort for developing personalized, point-of-care medical technologies. Such systems have unprecedented potential when matched with the newest developments in robotics, microprocessing, and tissue engineering. In this review, we present their emergence in medicine within the fields of diagnostics, biosensing, therapeutics, and theranostics. Discussion includes current limitations and future directions for these systems, as commensurate advances in power density and electronic processing are continually redefining the possible. As the research and funding attention coincide with complementary technological breakthroughs, the field is expected to grow into an advanced toolset for preserving human health. WIREs Nanomed Nanobiotechnol 2017, 9:e1455. doi: 10.1002/wnan.1455.