The rates of suicide attempts and death by suicide vary considerably over the lifespan, highlighting the influence of different contextual, risk, and protective factors at different points in development (Daniel & Goldston, 2009). Hopelessness and lack of connectedness to others are two factors that have been associated with increased risk for suicidal thoughts and behaviors across the lifespan. The primary purposes of this paper are to describe how hopelessness and lack of connectedness to others may contribute to risk for suicidal behaviors, and to outline empirically supported cognitive-behavioral interventions for these difficulties at three developmental periods during which suicidal behavior is prevalent: (a) adolescence and young adulthood, (b) middle adulthood, and (c) older adulthood. This paper is not intended as an exhaustive review, but rather an overview of selected developmental issues related to hopelessness and lack of connectedness to others as risk factors for suicidal behavior. Special emphasis is given to clinical implications for cognitive-behavioral interventions, which are illustrated through case conceptualizations and examples at each developmental period.