The p-factor is a construct that is thought to explain and maybe even cause variation in all forms of psychopathology. Since its 'discovery' in 2012, hundreds of studies have been dedicated to the extraction and validation of statistical instantiations of the p-factor, called general factors of psychopathology. In this Perspective, we outline five major challenges in the p-factor literature, namely that it: mistakenly equates good model fit with validity; corroborates weak p-factor theories through underspecified construct validation efforts; produces poorly replicated general factors of psychopathology; violates assumptions of latent variable models; and reifies general factors of psychopathology as latent, causal entities. In turn, the p-factor literature neglects alternative models that are incompatible with the notion that a single dimension adequately summarizes variation in all forms of psychopathology. These challenges raise questions about substantive interpretations of the p-factor, undermining confidence that the p-factor is a real, latent entity, or that general factors of psychopathology are useful summaries of psychopathology variation. We conclude with ways to move forward, in the spirit of strengthening the p-factor literature and improving psychopathology classification, treatment and prevention across the lifespan.