Lactation initiation refers to a functional change in the mammary organ from a non-lactating state to a lactating state, and a series of cytological changes in the mammary epithelium from a non-secreting state to a secreting state. Like the development of the mammary gland, it is regulated by many factors (including hormones, cytokines, signaling molecules, and proteases). In most non-pregnant animals, a certain degree of lactation also occurs after exposure to specific stimuli, promoting the development of their mammary glands. These specific stimuli can be divided into two categories: before and after parturition. The former inhibits lactation and decreases activity, and the latter promotes lactation and increases activity. Here we present a review of recent progress in research on the key factors of lactation initiation to provide a powerful rationale for the study of the lactation initiation process and mammary gland development.