Aminopeptidase N (APN) is an important metalloenzyme. It regulates multivariate cellular functions by different mechanisms such as enzymatic cleavage of peptides. This may play a role in endocytosis and regulate signal transduction. APN, a member of the M1 zinc metallopeptidase family, plays crucial roles in a variety of functions such as migration and invasion, and angiogenesis and metastasis of tumor cells. Therefore, APN inhibitors may be useful for the treatment of cancer. In this Perspective, structure-activity relationships of APN inhibitors are discussed to get an idea of possible lead candidates. APN inhibitors should possess an aryl hydrophobic function along with a zinc binding group attached to the hydrophobic group(s) to achieve high potency. This and other design aspects of APN inhibitors are discussed in this Perspective.