The prevalence of mental health disorders is rising with the coronavirus of 2019 pandemic, and millions of Americans reside in areas with mental health professional shortages. Primary care providers have an opportunity to provide care for commonly occurring mental health disorders. Using a holistic conceptualization of recovery in mental illness, this report provides evidence-based guidance for initiation, titration, and discontinuation of pharmacotherapy for mild to moderate depression and anxiety in the primary care setting. The use of measurement-based care, selection of appropriate class and agent for individual candidates, and patient education are addressed. Best practices for troubleshooting, titration, and referral are discussed.