Neurotrophins, which play crucial roles in the central nervous system (CNS), can act as both survival and death signals through their interaction with distinct receptors. Mature neurotrophins bind to Trk receptors, promoting neuronal survival and enhancing synaptic plasticity, while proneurotrophins, which are precursors of mature neurotrophins, bind to the p75 neurotrophin receptor (p75NTR) and induce cell death. The proteolytic cleavage of proneurotrophins into mature neurotrophins is a key regulatory mechanism that controls the direction of neurotrophin action. Recent studies have highlighted the 'yin and yang' nature of neurotrophin activity, where the same molecules can have opposing effects depending on their form and the receptors they activate. This model has significant implications for understanding the diverse cellular processes regulated by neurotrophins, including cell survival, synaptic plasticity, and structural changes in synapses. The regulation of proneurotrophin secretion, intracellular versus extracellular cleavage, and the role of specific proteases such as plasmin and tPA in controlling neurotrophin activity are also discussed. The bidirectional regulation of synaptic plasticity by pro- and mature neurotrophins, particularly in the hippocampus, is a key area of ongoing research, with potential implications for understanding and treating neurological disorders.Neurotrophins, which play crucial roles in the central nervous system (CNS), can act as both survival and death signals through their interaction with distinct receptors. Mature neurotrophins bind to Trk receptors, promoting neuronal survival and enhancing synaptic plasticity, while proneurotrophins, which are precursors of mature neurotrophins, bind to the p75 neurotrophin receptor (p75NTR) and induce cell death. The proteolytic cleavage of proneurotrophins into mature neurotrophins is a key regulatory mechanism that controls the direction of neurotrophin action. Recent studies have highlighted the 'yin and yang' nature of neurotrophin activity, where the same molecules can have opposing effects depending on their form and the receptors they activate. This model has significant implications for understanding the diverse cellular processes regulated by neurotrophins, including cell survival, synaptic plasticity, and structural changes in synapses. The regulation of proneurotrophin secretion, intracellular versus extracellular cleavage, and the role of specific proteases such as plasmin and tPA in controlling neurotrophin activity are also discussed. The bidirectional regulation of synaptic plasticity by pro- and mature neurotrophins, particularly in the hippocampus, is a key area of ongoing research, with potential implications for understanding and treating neurological disorders.