The procurement of lots of bovine serum that are free of infectious bovine viral diarrhea virus (BVDV) and of neutralizing antibodies to BVDV can still be problematic for manufacturers of biologics. For cell-culture based applications requiring the use of bovine serum as a cell culture medium supplement, the BVDV issue has plagued the industry for decades. Has there been any improvement over the years? The literature from the past four decades has been reviewed to answer this question. There is some evidence that the frequency of detection of infectious BVDV in commercial bovine serum lots has decreased in recent years. There are, however, insufficient data for making conclusions in the case for neutralizing antibodies to BVDV. There are several complementary approaches for mitigating the risk of introducing infectious BVDV into a manufacturing process. These include eliminating the use of serum, pre-treatment of the serum by the vendor or end-user, or treatment of media formulated with the serum to inactivate any BVDV that might be present.