Bioactive drugs are small molecules that can bind therapeutic targets like enzymes, proteins, and receptors and modulate their biological activities. Effective binding between bioactive drugs and receptors in vivo or in vitro is key to constructing useful tools in biomedical research and diagnosis. Molecular imprinting within surface/core cross-linked micelles was shown to afford water-soluble nanoparticle receptors for bioactive drugs. The molecularly imprinted nanoparticles obtained resembled proteins in size and were easy to prepare and very stable in adverse temperature or pH conditions. Strong imprinting effects were consistently observed for different bioactive molecules including alkaloids, folic acid, nonsteroidal anti-inflammatory drugs (NSAIDs), and catecholamines, in comparison to nonimprinted nanoparticles without the templates during the preparation. Fluorescent molecularly imprinted nanoparticles were also used as sensors for NSAIDs and catecholamines.