Inflammation is a well-characterized process used by the immune system as a component of the response to infection or tissue damage. The repertoire of signals used in immune inflammation, however, is neither limited to immune cells nor confined to adverse health events. Inflammatory signals affect mammogenesis, lactogenesis, lactation, and involution, often in dramatic ways. The role of inflammatory mediators in lactogenesis should not be surprising, given that lactogenic factors such as prolactin and growth hormone utilize cytokine receptors with second messengers that overlap with inflammatory cytokine signaling pathways. Some eye-opening studies have demonstrated that tissue-specific gene knockout mice lacking certain inflammatory mediators completely lack a functional mammary gland. Inflammatory signals are also critical mediators of mastitis-induced decreases in milk synthesis. Evidence for this role ranges from the molecular to the whole-animal level, implicating pattern recognition receptors which trigger inflammatory transcription factors that act as transcriptional repressors for milk synthesis genes. A poorly understood mechanism that contributes to this phenomenon is the transient but dramatic change in methylation of milk component gene promoters, which may or may not revert completely to the pre-mastitis condition after resolution of the inflammation. Conditional knockout mouse models demonstrated that inflammatory mediators such as interleukin-6 are essential for normal mammary involution at the end of lactation. More recent findings demonstrated that the loss of phagocytic cleanup of mammary tissue during involution (triggered by inflammatory signals) dramatically impairs milk production in the subsequent lactation. In closing, emerging data suggest that cellular differentiation processes, including those in the mammary gland, often incorporate inflammatory signaling, and inflammatory links with mammary development likely continue to operate into at least the very early stages of lactation.