Modern end-to-side (ETS) nerve transfers have undergone several permutations since the early 1990’s. Preclinical data have revealed important mechanisms and patterns of donor axon outgrowth into the recipient nerves and target reinnervation. The versatility of ETS nerve transfers can also potentially address several processes that limit functional recovery after nerve injury by babysitting motor end-plates and/or supporting the regenerative environment within the denervated nerve. Further clinical and basic science work is required to clarify the ideal clinical indications, contraindications, and mechanisms of action for these techniques in order to maximize their potential as reconstructive options.