Neotic preference refers to the extent to which animals prefer stimuli of differing novelty value. Degree of novelty is determined by within- and between-trials habituation and amount of temporal (novelty) and spatial change (complexity) in stimulation which in turn will determine the amount of curiosity-based approach (neophilia) or fear-based avoidance (neophobia) of novel stimuli. Tests of genuine neotic preferences enable direct assessments of responsiveness to temporal and spatial changes and include measurements of novel versus familiar locations (such as novelty-related location preferences), responsiveness to stimulus complexity (such as object exploration) and learning for exploratory rewards (such as light-contingent bar-pressing). Effects of brain lesions and peripherally administered drugs have implicated several brain areas and neurotransmitters that subserve memory, fear and reward in neotic preferences namely the hippocampus and ACh (memory), the amygdala, GABA and 5-HT (fear), and the mesolimbic DA reward system. However, more attention should be paid to the complexity of interactions between different brain and neurotransmitter systems and improvements in methodology before conclusions should be drawn about the neurobiological basis of neotic preferences.