Hopelessness is a painful cognitive state that is related to depression and suicide. Despite its importance, only unsystematic efforts have been made to specifically target hopelessness in interventions, and no comprehensive review is currently available to guide future clinical studies. In this narrative review, we first analyze the phenomenon of hopelessness, by highlighting its components (e.g., dismal expectations, blocked goal-directed processing, and helplessness), antecedents (e.g., inferential styles), and contextual factors (e.g., loneliness and reduced social support). Then, we review the currently available interventions and manipulations that target these mechanisms, either directly or indirectly, and we highlight both their strengths and lacunae. Finally, we propose possible avenues to improve our clinical toolbox for breaking the vise of hopelessness.