Clinical science seems to have reached a tipping point. It appears that a new paradigm is beginning to emerge that is questioning the validity and utility of the medical illness model, which assumes that latent disease entities are targeted with specific therapy protocols. A new generation of evidence-based care has begun to move toward process-based therapies to target core mediators and moderators based on testable theories. This could represent a paradigm shift in clinical science with far-reaching implications. Clinical science might see a decline of named therapies defined by set technologies, a decline of broad schools, a rise of testable models, a rise of mediation and moderation studies, the emergence of new forms of diagnosis based on functional analysis, a move from nomothetic to idiographic approaches, and a move toward processes that specify modifiable elements. These changes could integrate or bridge different treatment orientations, settings, and even cultures.