To navigate complex environments, animals must generate highly robust, yet flexible, locomotor behaviors. For example, walking speed must be tailored to the needs of a particular environment. Not only must animals choose the correct speed and gait, they must also adapt to changing conditions and quickly respond to sudden and surprising new stimuli. Neuromodulators, particularly the small biogenic amine neurotransmitters, have the ability to rapidly alter the functional outputs of motor circuits. Here, we show that the serotonergic system in the vinegar fly, Drosophila melanogaster, can modulate walking speed in a variety of contexts and also change how flies respond to sudden changes in the environment. These multifaceted roles of serotonin in locomotion are differentially mediated by a family of serotonergic receptors with distinct activities and expression patterns.