The smart sensor chip for simultaneous detection of a large number of disease markers is the most recent interest in the field of nanobiotechnology. Potential applications include miniaturized sensors to detect biological agents and diseases, biocompatible and improved systems for drug delivery. They are the simplest biomicroelectromechanical system (BioMEMS) devices that offer a very promising future to the development of novel physical, chemical and biological sensors. They can simultaneously detect a large number of antigens, antibodies, DNA molecules, trace metals, hormones, proteins, gases, microorganisms, toxins, chemical warfare agents, explosives etc. in gaseous, vacuum and liquid medium. Smart sensor chips would be of greater use in intensive care units (ICUs) where multiple disease markers are to be assessed precisely in very less time. These sensors employ highly specific biochemical reactions between complementary biomolecules in the same way that nature has used in our body to detect, diagnose and treat various types of diseases. They have aroused considerable interest because of their high specificity, ultra-high sensitivity, simplicity, low cost, less analyte requirement (in μl), less steps involved, non-hazardous procedure, quick response, low power requirement and a unique capability of detecting a large number of analytes simultaneously in a single step.