Psychological adjustment to catastrophic injuries and illnesses is a topic of much interest for practitioners providing clinical rehabilitation services. Depression and anxiety symptoms are associated with negative outcomes among individuals with SCI including lower functional independence, more secondary complications, and less community and social integration (Fann et al., 2011; Paul Kennedy & Rogers, 2000). This chapter attempts to summarize evidence garnered from SCI research that has investigated the management of post-SCI mental health potentially affecting successful adjustment to SCI. Though limited, these findings can assist in developing a foundation for evidence-based practice, and hopefully lead to improved and more consistent care. It should be emphasized, however, that evidence-based practice constitutes more than the routine use of treatments supported by the best research evidence available. Such practice also necessitates that the practitioner employs his or her clinical judgment in determining the applicability of such research conclusions to the treatment provided for each patient.