Depression is a complex disorder that is most likely the result of multiple sources of genetic vulnerability interacting with various environmental factors. Initially, depression is associated with stressful lifetime events, but what begins as a stress-sensitive process may manifest in an autonomous manner as the brain changes over time. This brief summary discusses the pathophysiology of depression and the potentially damaging effects that depression has on the function of neurocircuits in the brain and on structures such as neurons and their supportive neuroglia.