This presentation blends state of the science research on biomarkers of secretory activation and coming to volume in breast pump-dependent mothers of premature infants with pragmatic clinical practice strategies. Embedded in this approach is evidence that the mammary gland undergoes essential programming during the first two weeks postpartum, which can be measured with biomarkers, and is essential to long-term mothers’ own milk (MOM) provision. Clinical strategies that target the early postpartum period will be highlighted, including species-specific mammary gland stimulation, monitoring of MOM biomarkers of secretory activation and assessment of coming to volume. Additionally, the distinction between impaired secretory differentiation and delayed/impaired secretory activation in this population will be discussed, with application to NICU mothers who have multiple inflammation-based morbidities that increase the risk for lactation problems.