Suicide is a significant public health concern, particularly among primary care patients, given that many individuals who die by suicide visit their primary care provider in the months prior to their death. We examined constructs from two prominent theories of suicide, the interpersonal and psychache theories, including thwarted belongingness, perceived burdensomeness, and psychache. Among our sample (n = 224) of patients, perceived burdensomeness and psychache, individually and in serial, mediated the relation between thwarted belongingness and suicidal behavior. Thwarted belongingness was associated with greater perceived burdensomeness and, in turn, with more psychache and increased suicide risk. Our results elucidate the associations between the interpersonal and psychache theories of suicide. Clinical strategies that may reduce thwarted interpersonal needs and psychache, and which are appropriate for medical settings, are discussed.