With “Spatial Reference Frames” we refer to systems of coordinates by which the central nervous system encodes the relative positions of objects in space, including that of the body itself. A reference system is a way of representing the positions of the subjects / objects in space. The spatial position of an object can be represented in the brain with respect to different classes of reference points, which may be related or not to the position of the subject. In a nutshell, we can say that there are two types of transformations of space imagery: the allocentric spatial transformations, that involve a system of representation from object to object and encode information about the location of an object or its parts in relation to other objects, and egocentric spatial transformations that involve a system of subject-object representation. The human being switches from one code to another, depending on the contingent requirements, giving preference to one or another system according to a set of heterogeneous factors. The gender difference (male / female), for example, plays a key role. Even the individual cognitive strategies make use of different representations in a significantly different way. Manipulation of spatial reference systems constitute a “transnosographic trait” in various neurological and psychiatric disorders. Each of these diseases (autism, schizophrenia, epilepsy, spatial anxiety, Parkinson) reaches some of the structures involved in the manipulation of referential of different spaces. The chapter illustrates Piaget's study on the representation of space in the child and the use of different spatial coding systems, and provides a brief overview of the scientific debate following the Piagetian position.