Substance use disorders (SUDs) are chronic-relapsing conditions with remarkably high prevalence and staggering social costs. As a cluster of disorders, they are characterized by craving for drugs and loss of control over drug craving and drug taking behavior. In this talk, I will present select findings from my research program on SUDs, utilizing a variety of basic, clinical, neuroscience, computational, and translational methods. First, I’ll share a recent meta-analysis demonstrating that craving predicts drug use and relapse, underscoring its role as a target of treatment. I will then share neuroimaging findings using meta-analysis and machine learning, identifying brain regions most consistently implicated in craving and revealing a multivariate pattern that can predict craving in new participants from their brain activity. This pattern can also accurately distinguish drug users from non-users – across multiple types of SUDs – thus serving as a neural marker for craving, and potentially as the first diagnostic neuromarker for SUDs. Next, I will describe our work investigating the cognitive and neural mechanisms underlying the regulation of craving across drug types and regulation strategies. For example, I will demonstrate that regulation strategies drawn from cognitive-behavioral treatments rely on distinct neural mechanisms from mindfulness-based strategies. I will conclude with recent work developing novel digital interventions focused on the regulation of craving: a mechanism-focused intervention approach that is scalable and accessible for individuals who would not otherwise access traditional treatments. Along the way, I will highlight current applications of our work across other disorders and contexts, as well as my general approach to uncovering the neural mechanisms that underlie treatment-related change, across psychopathology.