Sirtuin 1 (SIRT1) plays an important role in regulating cellular physiological processes, such as metabolism, cell degeneration, cell growth, and cell survival. The recent reports showed that microRNAs (miRNAs) have emerged as the important regulators for cell proliferation, development, cancer formation, stress responses, cell death, and other physiological conditions in the past decade. More recently, miRNAs have revealed their prominent role in regulating gene expression and have provided new aspects of applications in diagnosis, prognosis, and therapeutic strategies in many human diseases. In the present review, we introduce and discuss the functions of SIRT1 and miRNAs. We also emphasize specific aspects of miRNAs that could modulate SIRT1-related signaling transduction and downstream effects, such as apoptosis, aging, and angiogenesis.