Heterotrimeric G proteins transduce signals from G protein-coupled receptors to regulate numerous signaling events and functions in airway smooth muscle (ASM). In this article, we detail the function and regulation of heterotrimeric G protein signaling in ASM. We further discuss recent advances in the development of experimental tools in the study of G protein signaling, and speculate how these tools might be used in therapeutic strategies that seek to mitigate bronchospasm and airway remodeling that occur in obstructive airway disease.