<p>Fetal bovine serum (FBS) is frequently used as a media supplement in cell cultures, as it contains many nutrients, growth factors, and hormones crucial to sustaining cell growth in vitro. However, over the years, concerns about its use have been highlighted. The unknown composition, batch-to-batch variability, and increasing demand and prices have raised scientific and economic issues. In addition, the collection procedure has raised ethical concerns. These issues have prompted researchers worldwide to explore more sustainable and reproducible alternatives performing like FBS. In this review, we examine several potential FBS substitutes, derived from other animal sources or chemically defined sera. Among the considered alternatives, milk emerges as a relevant and suitable option, helping to steer the biotechnological progress towards a more ethical and sustainable approach. Food waste is a globally widespread problem, and milk is no exception. Its use as an alternative supplement for cell cultures could contribute to a reduction in food waste and in the FBS usage, limiting the drawbacks associated with it. Furthermore, milk is often referred to as the “perfect food” as it is rich in nutrients fundamental to sustaining growth, resembling FBS characteristics. Bovine milk derivatives have proven effective in reducing and, in some cases, fully replacing FBS, therefore representing an interesting and feasible option as supplements for culture media. Considering that, requalified milk could help address both social and economic needs and, through circular economy strategies, reduce costs for the biotechnological industry and enhance environmental sustainability.</p>