<p>Perinatal mood and anxiety disorders (which include depression, anxiety and trauma-related conditions) affect one in five women during pregnancy and up to one year postpartum. Experiencing these conditions is one of the strongest predictors of perinatal suicidality, accounting for up to 25% of perinatal deaths globally. Evidence-based psychotherapies are highly effective at treating these common conditions, recommended by international guidelines and widely preferred over medications in perinatal populations. Improving access to psychotherapies might therefore be an effective preventive strategy to mitigate risk for perinatal suicidality. In this Review, we highlight mechanisms of change underpinning evidence-based psychotherapies for perinatal mood and anxiety disorders that might optimize delivery and increase access to quality care. We summarize the existing literature on the prevalence, manifestation and risk factors of perinatal depression, anxiety, post-traumatic stress disorder and suicidality, as well as evidence-based psychotherapies and their underlying mechanisms of change. Given the high comorbidity across diagnostic categories and the shared mechanisms of change among psychotherapies, we suggest a transdiagnostic approach to treating perinatal mood and anxiety disorders. Future research should rigorously test treatment-delivery innovations and measure potential mediators of treatment response to personalize care, optimize outcomes and prevent maternal death.</p>