Lactoferrin (LF) is an 80 kDa iron-binding glycoprotein primarily found in milk, saliva, tears, and nasal secretions. LF is well known for its antibacterial and immunomodulatory effects. However, the extraction of LF from milk is inadequate for large-scale therapeutic applications, presenting a challenge for economic mass production. Recombinant protein expression systems offer a solution to overcome this challenge and efficient production of LF. This review discusses recent progress in the translational research of LF gene transfer and biopharming, focusing on different expression systems such as bacteria, yeast, filamentous fungi, transgenic crops, and animals as well as purification methods. The optimization of expression yields, prospects for genetic engineering, and biotechnology to enhance LF production for biomedical applications are emphasized. This review systematically sourced the literature from 1987 to 2025 from leading scientific databases, including PubMed, Scopus, Web of Science, and Google Scholar. Despite ongoing debates, progress in this field indicates a viable path towards the effective use of LF in therapeutic settings.