Many cellular processes require a balance between protein synthesis and protein degradation. The vacuole/lysosome is the main site of protein and organellar turnover within the cell due to its ability to sequester numerous hydrolases within a membrane-enclosed compartment. Several mechanisms are used to deliver substrates, as well as resident hydrolases, to this organelle. The delivery processes involve dynamic rearrangements of membrane. In addition, continual adjustments are made to respond to changes in environmental conditions. In this review, we focus on recent progress made in analyzing these delivery processes at a molecular level. The identification of protein components involved in the recognition, sequestration, and transport events has begun to provide information about this important area of eukaryotic cell physiology.