The p-factor is relatively novel 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 5 major challenges in the p-factor literature, namely that it has: (1) mistakenly equated good model fit with validity; (2) sought to corroborate weak p-factor theories through underspecified construct validation efforts; (3) produced poorly replicated general factors of psychopathology; (4) violated assumptions of latent variable models; and (5) reified general factors of psychopathology as latent, causal entities, in turn neglecting alternative models that do not incorporate a p-factor and are entirely incompatible with the notion that a single dimension adequately summarizes variation in all forms of psychopathology. Each of these challenges raise questions about substantive interpretations of the p-factor (i.e., negative emotionality, thought disorder), undermining the field’s confidence that the p-factor is a real, latent entity, or that GFPs are useful summaries of psychopathology variation. We conclude with ways to move forward, in the spirit of strengthening the p-factor literature and improving our ability to classify, treat, and prevent psychopathology across the lifespan.