Comorbidity has presented a persistent puzzle for psychopathology research. We review recent literature indicating that the puzzle of comorbidity is being solved by research fitting explicit quantitative models to data on comorbidity. We present a meta-analysis of a liability spectrum model of comorbidity, in which specific mental disorders are understood as manifestations of latent liability factors that explain comorbidity by virtue of their impact on multiple disorders. Nosological, structural, etiological, and psychological aspects of this liability spectrum approach to understanding comorbidity are discussed.