Invasive brain-machine interfaces can restore motor, sensory and cognitive functions. However, their clinical adoption has been hindered by the surgical risk of implantation and by suboptimal long-term reliability. In this Review, we highlight the opportunities and challenges of invasive technology for clinically relevant electrophysiology. Specifically, we discuss the characteristics of neural probes that are most likely to facilitate the clinical translation of invasive neural interfaces, describe the neural signals that can be acquired or produced by intracranial electrodes, the abiotic and biotic factors that contribute to their failure, and emerging neural-interface architectures.