Apolipoprotein B (apoB) is the essential protein required for the assembly and secretion of chylomicrons from the small intestine and VLDLs from the liver. These lipoproteins, as well as their remnants and LDL, play key roles in the transport of dietary and endogenously synthesized lipids throughout the body. However, they can be involved in the initiation of atherosclerotic lesions in the vessel wall. Therefore, it is not surprising that the assembly of apoB-containing lipoproteins in the small intestine and liver is a highly regulated process. In particular, cotranslational and posttranslational targeting of apoB for degradation, regulated largely by the availability of the core lipids carried in the lipoprotein, by the types of dietary fatty acids consumed, and by the hormonal milieu, determines the number of chylomicrons or VLDL that are secreted. In this review, we summarize both older and more recent findings on the pathways of apoB degradation, focusing on events in the liver.