Nanostructured materials can now be engineered with great precision and complexity as a result of advances in design and fabrication, and offer distinct advantages in many biosensing and biomedical applications. The materials most widely used in this field are semiconductors and noble metals. Each offers multiple length scales of nanostructuring that program their physicochemical properties for different biosensing applications. Here, nanostructured materials and their applications are reviewed together with semiconductors and noble metals, as well as hybrid materials that unite these two classes—all with the goal of linking performance characteristics to applications in biomedicine.