Giant molecular clouds (GMCs) are the primary reservoirs of cold, star-forming molecular gas in the Milky Way and similar galaxies, and thus any understanding of star formation must encompass a model for GMC formation, evolution, and destruction. These models are necessarily constrained by measurements of interstellar molecular and atomic gas, and the emergent, newborn stars. Both observations and theory have undergone great advances in recent years, the latter driven largely by improved numerical simulations, and the former by the advent of large-scale surveys with new telescopes and instruments. This chapter offers a thorough review of the current state of the field.