Synapses are the fundamental units of communication and information processing in the nervous system. They show remarkable functional autonomy, as well as speed of signaling, bidirectional plasticity, and diversity. Synapses shape complex network functions, such as learning, memory, pattern separation, pattern completion, and many others. Synaptic dysfunction is responsible for a wide range of neurological and psychiatric diseases. Many of these diseases are emerging as synaptopathies, but the precise disease mechanisms are unknown. Given their micron-scale small size and seemingly compact structure, synapses were generally thought to be functionally indivisible structures. However, with the advent of high-resolution electrophysiology and imaging techniques, it is increasingly clear that synapses harbor functionally specialized nanomodules. This expanding nanobiology of the synapse provides a new perspective on synaptic signaling. The novel insight gained from this work is critical to understand disease mechanisms and to guide the development of appropriate therapeutic strategies for major brain diseases ranging from neurodegenerative and neurodevelopmental disorders to neuropsychiatric disorders such as depression and schizophrenia.