In recent years, the leverage on available genetic information and a better understanding of the genetic bases of dyslipidemias has led to the identification of potential new avenues for therapies. Additionally, the development of new technologies has represented the key for developing novel therapeutic strategies targeting not only proteins (e.g. the monoclonal antibodies and vaccines) but also the transcripts (from Antisense Oligonucleotides (ASOs) to small interfering RNAs) or the genomic sequence (gene therapies).These pharmacological advances have led to successful therapeutic improvements, particularly in the cardiovascular arena since we are now able to treat rare, genetically driven, and previously untreatable conditions (e.g: familial hypertriglyceridemia or hyperchylomicronemia).In this review, the pre-clinical pharmacological development of the major biotechnological cholesterol lowering advances will be discussed, describing facts, gaps, potential future step forwards and therapeutic opportunities.