Postnatal depression is a major source of morbidity among women who have recently delivered a child. Considering its high prevalence and serious negative consequences, prevention should be a high priority. A comprehensive synthesis of current knowledge of prevention strategies is important for clinical practice and future research. Searches of MEDLINE and PsychINFO were performed to identify English-language articles of randomized, controlled trials published from 1990 to 2003 focusing on primary prevention of postnatal depression in both the general and high-risk populations. Nineteen studies meeting these criteria were identified. The main findings and limitations of each study are documented. While the results are mixed, several of the studies provide support for the role of midwife intervention for pregnant and postnatal women. There are also some data that support the efficacy of brief psychotherapy in primary prevention. Unfortunately, many of the studies suffer from shortcomings that may limit their generalizability. Data is also lacking on biological interventions. Directions for future research are discussed, and general recommendations for prevention of postnatal depression in clinical practice are made. The findings of this review indicate that despite the relatively brief history of work in this area, progress is being made in identifying possible prevention interventions.