Acute care and inpatient rehabilitation settings present unique challenges related to psychosocial functioning and mental health. Inpatient neuropsychologists are often required to employ evidence-based assessments and treatment strategies to address the needs of the patients, teams, and clinical environment. This chapter addresses psychiatric issues commonly encountered in inpatient settings such as adjustment difficulties, acute stress, and risk for self-directed violence, as well as sleep disturbance and pain—two comorbidities that impact emotional well-being. We also review appropriate psychological measures to assess these issues, along with evidence-based psychotherapeutic interventions and clinical recommendations.