Psychotropic medications are chemical substances that cross the blood-brain barrier to exert their actions on neurons in the brain, and in doing so, they can alter mood, thought processes, and behavior. They are often prescribed to treat co-occurring psychological disorders in autism spectrum disorder. However, psychotropic medications are frequently observed to be prescribed to those with autism in the absence of a psychological disorder diagnosis. One predictor of psychotropic medication use in those with autism is destructive behavior. This chapter reviews psychotropic medications commonly prescribed to address destructive behavior in autism and the effectiveness of these medications in reducing these behaviors, including treatment durability (i.e., long-term use). Additionally, research examining the impact of psychotropic medication on various dimensions of destructive behavior will be discussed, as well as the factors that may influence the stability and durability of psychotropic medication use. Considerations for practice and future research will be provided.