First responders are vulnerable to the same psychiatric conditions and symptoms that affect the general population. However, they are particularly vulnerable to certain conditions by virtue of the stressful, often traumatic nature of their work environment. This includes disorders such as posttraumatic stress disorder and acute stress disorder, as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth edition, Text Revision (DSM-5-TR) (American Psychiatric Association [APA], 2022). This chapter will address the treatment of the most common disorders and symptoms that first responders are likely to experience. We will focus on the treatment of first responders who, despite their symptoms, are continuing to work. In some cases, the symptoms may cause so much distress or impairment that the first responders may need to take a leave of absence for treatment. A common thread in this chapter will be the importance of choosing medications that are safe to use in this population. For example, wherever possible, the use of a controlled substance that could lead to, or exacerbate, addictions will be avoided, or recommended with great caution. Second, medications that could cause intolerable side effects and interfere with the first responder's work will also be avoided or used sparingly. Sedation occurring during the work shift hours is an example of such a side effect. We will not address the treatment of psychotic disorders, such as schizophrenia or schizoaffective disorder in this chapter, since the presence of these disorders is thought to be uncommon in high-functioning individuals such as first responders and other professionals. While it is possible that an actively working first responder could develop a psychotic illness that would later interfere with their work and require treatment, we will not address these disorders due to their relative rarity in this population. We will, however, touch upon the use of antipsychotics in other conditions, for example, as augmenting agents in depressive disorders, or for the treatment of severe anxiety, usually in combination with other medications, or their use as mood stabilizers. We will not go into depth in this chapter on the diagnostic criteria for the various disorders, focusing more on a practical approach to pharmacologic treatment once the diagnoses have been established. For diagnostic criteria, we refer the reader to DSM-5-TR (APA, 2022) and the Comprehensive Textbook of Psychiatry (10th ed.) (Sadock et al., 2017).