Today, albumin, or a combination of saline and albumin, is used and widely accepted as a replacement for routine plasma exchange. However, decreased availability (due to market recalls secondary to Creutzfeld-Jacob or bacterial contamination risk) rising costs, recognition of drug interactions with albumin (i.e., ACE inhibitors) and a fear of disease transmission have led several groups to reconsider the use of colloid starches as partial or full replacement for plasma during plasma exchange. There are two hydroxyethyl starches: hetastarch (Hespan and Pentaspan) currently licensed for human use in the United States. While both are approved for granulocyte collection only Hespan is approved as a plasma volume expander. Anecdotal experience and limited reports in the literature with the use of starches as a replacement for plasma exchange suggest that such starch products are a reasonable replacement for albumin as an initial wash-out fluid or in combination with either albumin or saline. Kinetic modeling of the wash-out of starch used as a replacement fluid demonstrate that relatively little residual starch remains compared to the total amount infused. Hydroxyethyl starches are biochemically similar to glycogen, which likely explains the lack of immunogenicity and lack of adverse reactions. Substantial cost savings are associated with the substitution of starch for albumin. It is concluded that HES is well-tolerated and cost-effective as full or partial volume replacement with plasma exchange. It is anticipated that the use of HES will emerge as a standard of care in apheresis.