This chapter focuses on the embryo's bioactive secretome. It provides a brief overview of the early developments in the field, an analysis of the current state of development of diagnostic markers for embryo development and discusses the limitations in their development. There is an active bi-directional dialog between the embryo and the female reproductive tract which commences soon after fertilization. Embryo-derived potent platelet-activating factor (Paf) was capable of inducing a transient thrombocytopenia in peripheral blood within hours of fertilization in a range of species, and also sometimes caused a rebound thrombocytosis. Paf acts on a membrane receptor as early as the zygote stage to induce characteristic transient increases in the embryo's cytoplasmic calcium concentration. The chapter also provides a personal perspective of the future challenges to development and considers the broader benefits and risks that may accrue from a detailed analysis of the embryo's secretome.