Cells form and release multiple distinct classes of membrane-enclosed packets of information, collectively referred to as extracellular vesicles (EVs), to communicate with other cells located within their immediate surroundings or at a distance. This form of intercellular communication has been attracting a good deal of attention due to the critical roles it plays in development, tissue function/homeostasis, and when deregulated in the progression of diseases, including cancer. For example, the EVs produced by highly aggressive cancer cells have been shown to promote the growth, therapy-resistance, and invasiveness of other cancer cells. These same EVs can also travel through the circulation to future distant sites of metastasis and prepare them for the eventual arrival of cancer cells. However, several important questions regarding EV biology remain, including what are the mechanisms that regulate their production and how do these vesicles mediate their effects? The Antonyak and Weiss laboratories have teamed up and discovered that loss of the expression of the NAD-dependent deacetylase and tumor suppressor sirtuin 1 (SIRT1) in breast cancer cells results in the increased production of EVs containing unique protein cargo that promote aggressiveness phenotypes. The mechanism underlying this effect involves a previously unappreciated ability of SIRT1 to regulate the stability of RNA transcripts encoding potentially critical determinants of breast cancer progression. Here, we will build upon these exciting findings by further understanding how the loss of SIRT1 alters the expression of genes involved in EV biogenesis and determine the functional consequences these changes have on cancer progression.