Age-related changes in neural circuits, neural networks, and their plasticity are central to our understanding of age changes in cognition and brain structure and function. This paper summarizes selected findings on these topics presented at the Cognitive Aging Summit II. Specific areas discussed were synaptic vulnerability and plasticity, including the role of different types of synaptic spines, and hormonal effects in the dorsolateral prefrontal cortex of nonhuman primates, the impact of both compensatory processes and dedifferentiation on demand-dependent differences in prefrontal activation in relation to age and performance, the role of vascular disease, indexed by white matter signal abnormalities, on prefrontal activation during a functional magnetic resonance imaging-based cognitive control paradigm, and the influence of amyloid-β neuropathology on memory performance in older adults and the networks of brain activity underlying variability in performance. A greater understanding of age-related changes in brain plasticity and neural networks in healthy aging and in the presence of underlying vascular disease or amyloid pathology will be essential to identify new targets for intervention. Moreover, this understanding will assist in promoting the utilization of existing interventions, such as lifestyle and therapeutic modifiers of vascular disease.