Sensory substitution refers to the use of one sense to pick up information normally gathered by another sensory organ. With recent technological advances and scientific progress, sensory substitution appears as an interesting alternative for restoring some functions of a defective sensory organ (e.g., the sight in case of blindness). At the same time, our knowledge about cognitive and brain mechanisms involved in sensory substitution has grown considerably, bringing new insights into human perception and neural plasticity. From this perspective, sensory substitution can be considered as both a tool to investigate human cognition and brain functions, and a research topic in its own right. This paper addresses some of the major questions raised by sensory substitution, demonstrates how the study of sensory substitution enhances our understanding of human perception and brain plasticity and provides an overview of rehabilitation potentialities.