Neuroplastic changes in somatotopic organization within the motor and somatosensory systems have long been observed. The interruption of afferent and efferent brain-body pathways promotes extensive cortical reorganization. Changes are majorly related to the typical homuncular organization of sensorimotor areas and specific "somatotopic interferences". Recent findings revealed a relevant peripheral contribution to the plasticity of body representation in addition to the role of sensorimotor cortices. Here, we review the ways in which structures and brain mechanisms react to missing or critically altered sensory and motor peripheral signals. We suggest that these plastic events are: (i) variably affected across multiple timescales, (ii) age-dependent, (iii) strongly related to altered perceptual sensations during and after remapping of the deafferented peripheral area, and (iv) may contribute to the appearance of secondary pathological conditions, such as allodynia, hyperalgesia, and neuropathic pain. Understanding the considerable complexity of plastic reorganization processes will be a fundamental step in the formulation of theoretical and clinical models useful for maximizing rehabilitation programs and resulting recovery.