Introduction: Plasmapheresis has been used with different levels of evidence in neurology, nephrology, and rheumatology. Management guidelines have evolved with the development of randomized clinical trials; however, the low prevalence of some conditions that can benefit from this intervention is a limitation. Objective of the review: This article is a narrative review that reviews the basic principles of plasma exchange therapy, establishes the levels of evidence, and identifies entities that may benefit from this treatment. Essential points of the review: In category I, the conditions are established where the therapy is first-line; in category II, plasmapheresis is the second treatment option; in category III, the optimal role has yet to be established; and in category IV, it is an ineffective treatment. Among the category I renal indications are Goodpasture syndrome with diffuse alveolar hemorrhage, recurrent focal and segmental glomerulosclerosis in kidney transplant, vasculitis associated with ANCA, rapidly progressive, ABO incompatible kidney transplant. Conclusion: Due to the lack of clinical studies, some pathologies remain with indications category II to IV. Due to the low prevalence and incidence in intensive care, the collective work of the scientific community is required.