This chapter reviews the biology of neurotrophins (NTs) and their receptors with an emphasis on their use to encourage nerve regeneration after damage to both the central and peripheral nervous system. NTs bind to a receptor complex comprised of two components: p75 and a tropomyosin-related kinase (Trk) transmembrane receptor protein tyrosine Kinase. Ligand binding induces Trk subunit dimerization and the autophosphorylation of multiple tyrosine residues. This autophosphorylation initiates several different intracellular signaling cascades that are described in the chapter. p75 can also play an important role as a negative regulator of axon growth by virtue of its interactions with the rho GTPase. Damaged peripheral axons undergo a characteristic sequence of morphological and physiological changes. The specificity of different NTs in promoting regeneration of different functional classes of dorsal root (DR) fibers suggests that spinal axons should also be selectively responsive to different NTs.