The aim in this review article is to document research findings that have shown paradoxical effects of nervous system changes, whereby direct or indirect neural damage may result in facilitation of behavioural functions. Such findings have often been ignored or undervalued in the brain-behaviour research literature. A further aim is to consider possible mechanisms and theoretical insights related to this facilitation. Analyses of relevant studies show that two major types of paradoxical functional facilitation (PFF) effects may be distinguished. (i) Situations where damage to intact brain tissue brings to normal or near normal a previously subnormal or abnormal level of functioning. I refer to improved levels of functioning in such contexts as restorative PFF effects. One of the best documented examples of such PFF effects is the ‘Sprague effect’, whereby collicular lesions may bring about an improvement in visual functioning following an initial occipital lesion. (ii) Situations where a subject with nervous system pathology or sensory loss performs better than normal control subjects on a particular task. I refer to improved levels of performance in these contexts as enhancing PFF effects. Restorative and enhancing PFF effects have been found in a range of domains, including memory, sensory and perceptual functions, and language functioning. A potential contribution of PFF effects is that they highlight two important neural mechanisms, i.e. inhibition and compensatory plasticity. Two broad classes of theoretical insights related to PFF effects are therefore discussed: (i) inhibitory mechanisms, which form part of an interactive view of brain function where competitive opponent-processing is a significant feature; (ii) ‘compensatory augmentation’, which occurs as a specific manifestation of CNS plasticity. Both of these mechanisms are considered in relation to paradoxical increases in CBF and anatomical annexation effects that are seen in neurological patients and in subjects with sensory loss. Paradoxical functional facilitation paradigms represent a powerful methodological tool for confirming or refuting hypotheses in brain-behaviour research. The counter-intuitive nature of PFF findings provides a particularly persuasive set of evidence in support of neural, conceptual or computational models of brain function that specifically predict paradoxical facilitation of cognitive functioning.