Electrochemical and optical sensors are useful probes for the detection of medically relevant analytes. For more sensitive drug detection, the properties of both of these devices are combined into a photoelectrochemical sensor (PECS). The photocatalytically generated current in a photoelectrochemical sensor is enhanced by different combinations of organic and inorganic semiconductors engineered onto the electrode surface. The effect of material morphology on the pharmaceutical detection performance of photoactive nanomaterials-based photoelectrochemical sensors, recent developments in the design of Bi2S3-based PECS for distinguishing single-base mismatch DNA sequences, and the characteristic features of photolithographically modified ITO electrodes by redox substrates for simultaneous multidrug detection are shared in this chapter. The protocols for a simultaneous competitive immunoassay for tetracycline and chloramphenicol on an electrode surface modified with CdS and PbS nanoclusters is presented. One of the important and more advanced developments in the design of highly sensitive PECS is the immobilization of quantum dots (QDs) at the electrode, which illuminate upon binding to the target analyte, resulting in a boost to the intensity of the photogenerated current. Therefore, this chapter covers recent developments in electrode modification with quantum dots for sensing the binding event of target pharmaceuticals, cancer biomarkers, and biologically important compounds, such as analytes. The role of CdSe QDs as a photosensitizer is highlighted. The details of light-emitting diodes (LEDs) based on ZnO nanorods as a cutting-edge multiplexed photoelectrochemical sensor for the detection of cancer biomarkers are presented. The sensing performance of less toxic Ag2S quantum dots for the photoelectrochemical detection of cancer biomarkers is discussed. Moreover, some challenges of QD-based photoelectrochemical sensors, such as the relatively low electrochemiluminescence (ECL) efficiency and the toxicity issues of QDs, which hamper their real-life applications, are addressed. Finally, future perspectives are offered in the context of QDs/biomolecule hybrid systems for advanced ECL drug analysis. © 2019 Elsevier Inc. All rights reserved.