Working memory is conceptually different from short-term memory and likely relies on different neurobiological substrates. Working memory may be defined as the capacity to use mnemonic information to plan and organize forthcoming action. These processes rely on the prefrontal cortex (PFC), and neurons in this region appear to encode mnemonic information and forthcoming responses based on memory. The task related activity of PFC neurons and overall working memory performance is strongly regulated by dopamine. Dopamine might bias networks of PFC neurons to enter different processing modes, causing PFC networks to either process memory related information in a flexible manner (state 1) or to strongly maintain a single goal state in memory even in the presence of distracters (state 2). Dopamine levels in PFC fluctuate during different cognitive and emotional states, and such fluctuations could switch PFC networks between these two states. Dopamine may therefore dynamically regulate how PFC networks “work with memory” to guide future thought or action.