The popularity of the zebrafish (Danio rerio) grows rapidly in translational neuroscience and neurobehavioral research. Physiological and genetic similarity to mammals (including humans), easiness of genetic and pharmacological manipulations, low cost, rapid development, and potential for high-throughput screening contribute to the growing utility of zebrafish as a model object in translational neuroscience. Locomotor activity is a core element of behavioral phenotype of zebrafish. Since alterations in locomotor behavior can serve as markers of various psychiatric and neurological diseases, studies on zebrafish locomotor behavioral patterns are highly useful for probing their potential genetic bases as well as for innovative drug screening. Here, we discuss major aspects of zebrafish locomotor behavior, its neural and genetic bases, and its relevance for translational neurobehavioral research.