Exchangeable apolipoproteins, composed mainly of amphipathic α-helices, are associated with various plasma lipoproteins and play an important role in the metabolism of those lipoproteins to which they bind. Accumulating experimental evidence suggests that exchangeable apolipoproteins, such as apoE, apoA-IV, and apoC-III, also play a role intracellularly in facilitating lipid recruitment at different stages of very low-density lipoprotein assembly and trafficking through the endoplasmic reticulum-Golgi secretory compartments. Experimental evidence also suggests that apoA-I may become lipidated intracellularly through mechanisms dependent on or independent of ATP-binding cassette transporter A1. Thus, expression of these secretory proteins may exert an impact on hepatic triglyceride and cholesterol homeostasis during their transit from the endoplasmic reticulum through the Golgi apparatus. This review summarizes findings related to the modulation of intracellular assembly of very low-density lipoprotein and high-density lipoprotein by exchangeable apolipoproteins.