It has been suggested that long-term modifications of synaptic transmission constitute the foundation of the processes by which information is stored in the central nervous system. A group of proteins called neurotrophins are considered powerful molecular mediators in central synaptic plasticity. Among these, brain-derived neurotrophic factor (BDNF) as well as neurotrophin-3 (NT-3) have emerged as having key roles in the neurobiological mechanisms related to learning and memory. In this chapter, we review the studies that have represented a significant step forward in understanding the role played by BDNF and NT-3 in long-term synaptic plasticity. The effects of BDNF and NT-3 on synaptic plasticity can be of a permissive nature, establishing the conditions under which plastic changes can take place, or it may be instructive, directly modifying the communication and morphology of synapses. The actions carried out by BDNF include its capacity to contribute to the stabilization and maturation of already-existing synapses, as well as to generate new synaptic contacts. One important finding that highlights the participation of these neurotrophins in synaptic plasticity is the observation that adding BDNF or NT-3 gives rise to drastic long-term increases in synaptic transmission, similar to the long-term potentiation in the hippocampus and neocortex of mammals. Because neurotrophins modulate both the electrical properties and the structural organization of the synapse, these proteins have been considered important biological markers of learning and memory processes.