Organoids can be derived from various cell types in the lung, and they provide a reproducible and tractable model for understanding the complex signals driving cell fate decisions in a regenerative context. In this review, we provide a retrospective account of organoid methodologies and outline new opportunities for optimizing these methods to further explore emerging concepts in lung biology. Moreover, we examine the benefits of integrating organoid assays with in vivo modeling to explore how the various niches and compartments in the respiratory system respond to both acute and chronic lung disease. The strategic implementation and improvement of organoid techniques will provide exciting new opportunities to understand and identify new therapeutic approaches to ameliorate lung disease states.