D-Serine modulates NMDA receptors and regulates synaptic plasticity, neurodevelopment, and learning and memory. However, the primary site of D-serine synthesis and release remains controversial, with some arguing that it is a “gliotransmitter” and others defining it as a “neuronal co-transmitter”. Results from several laboratories using different strategies now show that the D-serine’s biosynthetic enzyme, serine racemase (SR), is expressed almost entirely by neurons, with few astrocytes appearing to contain D-serine. Cell-selective suppression of serine racemase expression demonstrates that neuronal, rather than astrocytic D-serine, modulates synaptic plasticity. Here we propose an alternative conceptualization whereby astrocytes affect D-serine levels by synthesizing L-serine that shuttles to neurons to fuel the neuronal synthesis of D-serine.