The sensory brain areas of a sample of more than one hundred deep-sea fish species were studied and the relative volumes of the olfactory bulb, optic tectum, octavolateral area, and the gustatory area determined. In the absence of direct observations on the behavior of this ichthyofauna these data allow to make deductions about the kinds of sensory modalities used preferentially in the remote deep-sea environment. In the present chapter, members of three families are compared that have representatives living on or near the sea floor (“demersal”) and in the open water between 200 and 1,000 m (mesopelagic). The findings indicate that both regions present fish with rich and diverse sensory environments. While vision emerges as the dominant sense of the mesopelagic realm, olfaction seems more important on or near the bottom of the sea. However other sensory modalities supplement these senses in species-specific patterns. Considerations of the phyletic relationships indicate different degrees of pervasiveness. Whilst in slickheads the dominance of vision appears to be a family related trait, similar common features are found neither in the eels nor in the grenadiers. By contrast, the common trait in these two families seems to be the greater adaptability to the environment.