Sensors are devices that detect a physical, chemical, or biological stimulus and give a response in the form of a measurable signal. The increasing number of applications for sensing technologies has increased the need for the development of a variety of new sensors with far better performance. Nanoparticles are at the forefront in the fabrication of high-throughput nanosensors for applications ranging from pharmaceuticals to signature nano-based platforms that profile different therapeutic drugs, selective chemicals, and bioassays to environmental analysis by modifying the surface of the electrode for electrochemical detection, offering high sensitivity and selectivity. In this chapter, we will discuss the sensing enhancement impact of a number of nanoparticles, including metals, oxides, and semiconductor-based nanoparticles, mostly employing carbon-based nanoparticles (CNTs, graphene, fullerenes, carbon nanodots, nanowires, and nanodiamonds), dendrimers, and composite nanoparticles on multiple sensors, such as electrochemical, optical, and photoelectrochemical sensors. Moreover, this chapter will offer an introduction to recent developments in the design of nanosensors for trace-level multidrug detection with reproducible results. The ability of electrodes modified with nanomaterials for multianalyte screening and rapid toxicity testing will also be discussed. Moreover, owing to the unique oxidation or reduction potential of every drug, the selectivity of electrochemical sensing platforms based on nanomaterials for the detection of drugs and their metabolites will be highlighted. © 2019 Elsevier Inc. All rights reserved.