PURPOSE OF REVIEW: Lipoprotein apheresis is the most effective means of lipid-lowering therapy. However, it's a semi-invasive, time consuming, and chronic therapy with variable adherence. There are still no specific guideline recommendations for the management of patients on lipid apheresis. The purpose of this review is to discuss the clinical indications and major drawbacks of lipid apheresis in the light of recent evidence. RECENT FINDINGS: Lipoprotein apheresis should be initiated at early ages and performed frequently to receive the expected cardiovascular benefits. However, in clinical practice, most patients experience ineffective apheresis and fail to reach lipid targets. This real-world failure is due to several factors including late diagnosis, delayed referral, and improper frequency of procedures. All these denote that awareness is still low among physicians. Another important factor is the semi-invasive, time consuming nature of the apheresis, leading to high refusal and low adherence rates. Moreover, apheresis decreases quality of life and increases the risk of depression. Mental status is also deteriorated in patients with familial hypercholesterolemia on lipid apheresis. New effective lipid lowering agents are underway with promising cardiovascular results. To overcome the drawbacks, a structured approach, including standardized protocols for lipoprotein apheresis with regular cardiovascular follow-up is warranted. New effective lipid lowering agents with documented cardiovascular benefit, should be integrated into the treatment algorithms of patients on lipoprotein apheresis.