The domestication and improvement of maize resulted in radical changes in shoot architecture relative to its wild progenitor teosinte. In particular, critical modifications involved a reduction of branching and an increase in inflorescence size to meet the needs for human consumption and modern agricultural practices. Maize is a major contributor to global agricultural production by providing large and inexpensive quantities of food, animal feed, and ethanol. Maize is also a classic system for studying the genetic regulation of inflorescence formation and its enlarged female inflorescences directly influence seed production and yield. Studies on the molecular and genetic networks regulating meristem proliferation and maintenance, including receptor-ligand interactions, transcription factor regulation, and hormonal control, provide important insights into maize inflorescence development and reveal potential avenues for the targeted modification of specific architectural traits. In this review, we summarize recent findings on the molecular mechanisms controlling inflorescence formation and discuss how this knowledge can be applied to improve maize productivity in the face of present and future environmental challenges.