This chapter traces developments in American Protestant responses to mental illness. The professionalization of medicine, shifting theological emphases, and cultural forces shaped reactions that ranged from benign neglect by many to impassioned advocacy by a few. Christians enter the narrative in various roles: ministers, physicians, sufferers, family members, advocates, seminary professors, and a variety of mental health professionals. The identities of some spanned those categories. Across time, churchgoers and religious leaders deployed terms for distress that included distraction, possession, madness, melancholy, insanity, mental illness, and later, diagnostic terms such as depression, bipolar disorder, post-traumatic stress disorder, and schizophrenia. Regardless of labels, as individuals and groups of believers thought about mental illness, sought meaning, and responded amid distress, their context-specific claims of what seemed awry shaped assessments of how best to deploy available resources.