BACKGROUND A parenteral lipid emulsion (LE), used as a key source of energy, essential fatty acids (FAs), and fat-soluble vitamins, is an integral part of a parenteral nutrition (PN) regimen. The conventional LEs, such as soybean oil (SO)-based emulsions, have caused concerns about the potential adverse effects involving oxidative stress, inflammation, and immune response probably because of undesirable FA composition. METHODS Recently, alternative LEs, optimizing the FA composition with partial substitution of SO with medium-chain triglyceride (MCT), olive oil (OO), and fish oil (FO), have been developed and applied in clinical practice. This review summarizes the characteristics and beneficial clinical effects of alternative parenteral LEs in critically ill, pediatric, and long-term PN patients. CONCLUSIONS More clinical data from sufficiently high-powered studies are required to characterize the integral biological properties of alternative LEs for further selection to fit individual needs and disease characteristics. Simultaneously, potential lipid sources with desirable FA compositions and biological properties should be selected to develop new therapeutic LEs. As supplements to current parenteral lipids, the new LEs with different therapeutic effects are expected to fit specified subpopulations of patients with different diseases. Great efforts should be devoted to the development of parenteral LEs.