In this review, we summarize recent developments in nanobiosensors and their applications in biology and potential in medical diagnostics. We first highlight the concept of coordinated nanobiosensors, which integrate desirable properties of the individual components: protein machinery for sensitivity and specificity of binding, peptide or nucleic acid chemistry for aligning the various electron-transducing units and the nanoelectrodes for enhancing sensitivity in electronic detection. The fundamental basis of coordinated nanobiosensing is in applying the precise 3D atomic resolution structural information to rationally design and fabricate biosensors with high specificity and sensitivity. Additionally, we describe several biosensors developed for detecting biologically relevant compounds, including those for hydrogen peroxide, dopamine, glucose, DNA and cytochrome C. Results from these systems highlight the potential advantages of using nanoscale biosensors and how further developments in this area will change biomedical diagnostics and treatments drastically.