Vivid dreaming often conjures-up imaginary novel images during the sleep. Humans can also imagine novel mental images consciously and purposefully in the process of Prefrontal Synthesis (PFS). Despite both processes commonly referred to as ‘constructive imagination,’ their mechanisms of mental image creation are very different. PFS is completely dependent on the lateral prefrontal cortex (LPFC) and patients with damage to the LPFC often lose their PFS ability. Conversely, dreaming is not controlled by the LPFC: the LPFC is inactive during the sleep and patients whose LPFC is damaged do not notice any change in their dreams. Other neurobiologically distinct components of imagination discussed in this manuscript include amodal completion, categorically-primed spontaneous imagination, integration of modifiers and mental rotation, and Prefrontal Analysis. Clearer neurobiological definitions of separate imagination mechanisms can lead to better understanding of hominin evolution and better educational strategies in children with neurodevelopmental delays. J. Curr. Neurobiol. 10, 89–109 (2019).