In this chapter, we discuss the design and fabrication of flexible, micro- and nanoscale electronic devices for monitoring and manipulating the activity of excitable tissues. The cells within the brain, heart, and muscles rely on complex bioelectric signals to maintain proper function. Interfacing these types of tissues has been a challenge because the mechanical mismatch between traditional electrodes and the targeted tissue results in many undesirable side effects, such as inflammation and scarring. Nanomaterials represent a noninvasive alternative to the rigid and bulky electrodes used for the past decades. Here, we explore silicon-, carbon-, and polymer-based building blocks that can be assembled and integrated into devices, with demonstrated or potential capability of interfacing with and probing of excitable tissues. We also focus on how the leading pioneers of the field have addressed the many challenges encountered in the process of achieving clinically relevant device platforms.