Women with serious mood and psychotic disorders have historically been discouraged from breastfeeding due to limited safety data for psychiatric medications. However, current evidence suggests that most first- and second-generation antipsychotics are compatible with breastfeeding, with clozapine being the notable exception. This chapter examines evidence-based approaches to medication selection during breastfeeding, emphasizing that treatment decisions should be individualized based on maternal psychiatric history, infant health status, maternal preferences, clinical needs, and available lactation safety data. The decision-making process requires prioritizing maternal mental health and wellbeing while implementing measures to minimize infant exposure and monitor infant development. Rather than viewing maternal treatment and infant safety as competing priorities, this chapter advocates for a comprehensive care model that recognizes these objectives as interconnected elements of optimal perinatal psychiatric care.