Although therapeutic plasma exchange is known to be the most effective and efficient therapeutic modality for some disorders such as thrombotic thrombocytopenic purpura and hyperviscosity syndrome, no standard protocol of plasma exchange has been developed. A protocol based on evidence needs to be established for standard of care. It should include exchange volume, replacement fluid, frequency, and end point. Indication of plasma exchange is not always clear because prospective randomized clinical trials, especially blinded trials, are difficult to perform. The standard guideline is now available from Category 1 to Category 4 and is published by the American Association of Blood Banks and the American Society for Apheresis. Each institution should establish its own pheresis guideline and protocol for each disorder.