In contrast to animals, plants maintain life-long post-embryonic organogenesis from specialized tissues termed meristems. Shoot meristems give rise to all aerial tissues and are precisely regulated to balance stem cell renewal and differentiation. The phytohormone auxin has a dynamic and differential distribution within shoot meristems and during shoot meristem formation. Polar auxin transport and local auxin biosynthesis lead to auxin maxima and minima to direct cell fate specification, which are critical for meristem formation, lateral organ formation, and lateral organ patterning. In recent years, feedback regulatory loops of auxin transport and signaling have emerged as major determinants of the self-organizing properties of shoot meristems. Systems biology approaches, which involve molecular genetics, live imaging, and computational modeling, have become increasingly important to unravel the function of auxin signaling in shoot meristems.