Bilateral communication between bone and nerves is crucial for optimal repair of large bone defects as well as repair of peripheral nerves within the skeleton. However, simultaneous regeneration of bone and nerves is an issue that has long been overlooked in prior literature. Incongruous or even contradictory requirements or regeneration environments for bone and nerves make simultaneous regeneration of multiple tissues challenging. The present review commences with introducing natural crosstalk between bone and nerves, highlighting the rationale for simultaneous regeneration of bone and nerves. These issues will pave the way for the development of inspirational materials design concepts that capitalize on the principles of osteoconduction, osteoinduction, neuroconduction, neuroinduction, and neuroattraction. Potential strategies based on selection of appropriate scaffolds, acellular biological factors and architectural design will be addressed.