The article discusses the phenomenon of synaptic scaling, a form of homeostatic plasticity that adjusts the strength of excitatory synapses to stabilize neuronal firing rates. Synaptic scaling is detected by neurons through calcium-dependent sensors, which regulate receptor trafficking to increase or decrease the accumulation of glutamate receptors at synaptic sites. This process allows neurons to maintain stable firing rates in the face of changes in network activity or developmental modifications. The review highlights the cellular and molecular mechanisms underlying synaptic scaling, including the role of calcium/calmodulin-dependent protein kinases (CaMKs) and the immediate early gene Arc. It also explores the distinction between global and local forms of homeostatic plasticity, and the potential interactions between synaptic scaling and other forms of plasticity like long-term potentiation (LTP) and long-term depression (LTD). The article suggests that synaptic scaling operates through a graded, transcription-dependent process that continuously adjusts the steady-state number of receptors in the synaptic membrane. Additionally, it discusses the signaling pathways involved in synaptic scaling, such as brain-derived neurotrophic factor (BDNF) and tumor necrosis factor α (TNFα), and their potential roles in mediating the plasticity. The review concludes by emphasizing the complexity of the signaling pathways and receptor trafficking machinery involved in synaptic scaling, suggesting that it may be a push-pull mechanism where opposing processes titrate the level of neuronal firing.The article discusses the phenomenon of synaptic scaling, a form of homeostatic plasticity that adjusts the strength of excitatory synapses to stabilize neuronal firing rates. Synaptic scaling is detected by neurons through calcium-dependent sensors, which regulate receptor trafficking to increase or decrease the accumulation of glutamate receptors at synaptic sites. This process allows neurons to maintain stable firing rates in the face of changes in network activity or developmental modifications. The review highlights the cellular and molecular mechanisms underlying synaptic scaling, including the role of calcium/calmodulin-dependent protein kinases (CaMKs) and the immediate early gene Arc. It also explores the distinction between global and local forms of homeostatic plasticity, and the potential interactions between synaptic scaling and other forms of plasticity like long-term potentiation (LTP) and long-term depression (LTD). The article suggests that synaptic scaling operates through a graded, transcription-dependent process that continuously adjusts the steady-state number of receptors in the synaptic membrane. Additionally, it discusses the signaling pathways involved in synaptic scaling, such as brain-derived neurotrophic factor (BDNF) and tumor necrosis factor α (TNFα), and their potential roles in mediating the plasticity. The review concludes by emphasizing the complexity of the signaling pathways and receptor trafficking machinery involved in synaptic scaling, suggesting that it may be a push-pull mechanism where opposing processes titrate the level of neuronal firing.