Parental lifetime experience influences the health and well-being across generations. Maternal exposures are influential, but paternal exposures are emerging as playing an equally important role. While our understanding of the impact of paternal exposures on offspring health is increasing, the mechanisms underlying these changes remain to be fully defined. To date, studies have largely focused on genetic and epigenetic alterations to sperm cargo as the primary mechanism for the transmission of paternal experience. However, our recent findings demonstrate that non-germ cell factors are sensitive to paternal environmental stressors in a manner that may also influences fetal development and offspring health. Here, we discuss our recent research in mice that explores the influence of a variety of different paternal environmental exposure models, including obesity, heat and reproductive toxicants, on seminal fluid composition and function. Our studies demonstrate that the seminal vesicles, the primary contributor to seminal plasma in mice and most mammalian species, are sensitive to environmental insults. Across all exposure models, we provide evidence that the seminal vesicles respond through altering the composition of their secretions, including cytokines mediating male-to-female signalling at coitus. Using a paternal obesity model, we further demonstrate that these changes ultimately interfere with the establishment of an optimal female reproductive tract immune environment that is required to facilitate embryo implantation and reproductive success. These findings demonstrate that paternal exposures alter the composition of male seminal fluid, including, and raise the prospect that male seminal fluid signalling factors form a novel pathway that contributes to paternal programming.