Advancements in system-wide transcriptomic approaches have significantly benefited the study of salivary gland development, function, and dysfunction. Well before the importance of studying cells in their native context was widely appreciated, salivary gland researchers used organ explants and animal models to study salivary gland development and made significant contributions through the traditional, reductionist approaches. The applications of RNA-based systems biology approaches have now revolutionized this field. These approaches have enabled the profiling of all transcripts produced, initially at the whole organ level and currently at the single-cell level, to greatly enhance our understanding of the salivary glands. Initial studies used single-cell transcriptomic information to identify the cell types present in every type of salivary gland at multiple developmental stages. These data are now being used to elucidate the molecular mechanisms driving salivary glands development, regeneration, and recovery from injury to inform new therapeutics based on this understanding. The emergence of new technologies and analysis tools such as deep learning and artificial intelligence promises to have an even greater impact in the future. Here we review the history of how RNA-based technologies have influenced the study of salivary gland development and regeneration. Also, we provide an outlook on how new transcriptomic-based tools and technologies can enhance our understanding of glandular development and regeneration and facilitate future therapies for pathological conditions involving the salivary glands.