Despite the need for further prospective studies and clinical trials to test the efficacy of the psychobiological model of exercise as an intervention and treatment for SUD, physical exercise has been shown to be an effective and promising additional therapeutic tool for individuals with SUD. Here, we have described the brain areas affected by chronic substance use in patients with SUD as well as those improved by aerobic exercise. Some of these areas are primarily related to executive functions, which refer to a set of self-regulatory processes associated with the control of thoughts and behavior, including inhibitory control and decision-making. Therefore, in the same way that physical exercise is advised for treating other diseases, the neuroplasticity promoted by aerobic exercise may indicate its usefulness as a potential additional treatment for individuals with SUD. Specifically, these benefits may be seen in brain areas related to executive control, such as those areas involved in inhibition of drug-seeking behavior and impulsivity, as well as in decision-making regarding drug consumption. Furthermore, individuals with SUD who improve their fitness levels may enhance PFC function and cognition. These benefits should improve an individual’s ability to inhibit drug consumption behavior when exposed to environmental cues and, consequently, their ability to maintain abstinence. However, this is still a hypothesis, and further studies are necessary to provide evidence of the effectiveness of exercise on maintaining drug abstinence, specifically exercise of self-regulated intensity. Thus, we propose an integrative cognitive-psychobiological model of exercise for future research and provide practical guidance to optimize its potential benefits during rehabilitation programs.